Cancers

29 pages, 3572 KB

Open AccessReview

Fifty Shades of PSMA-Avid Rib Lesions: A Comprehensive Review

by Amirreza Shamshirgaran, Mohammad Hadi Samadi, Michael Saeed, Sara Harsini, Pegah Sahafi, Ghasemali Divband, Gholamreza Mohammadi, Narjess Ayati, Ramin Sadeghi, Alessio Rizzo, Giorgio Treglia and Emran Askari

Cancers 2025, 17(21), 3404; https://doi.org/10.3390/cancers17213404 (registering DOI) - 22 Oct 2025

Abstract

Background: While prostate-specific membrane antigen (PSMA)-targeted imaging has revolutionized metastatic detection, unspecific bone uptake (UBU)—particularly in the ribs—is a common but diagnostically challenging finding in prostate cancer (PCa) patients. This review aims to synthesize current evidence on PSMA-avid rib lesions in PCa and [...] Read more.

Background: While prostate-specific membrane antigen (PSMA)-targeted imaging has revolutionized metastatic detection, unspecific bone uptake (UBU)—particularly in the ribs—is a common but diagnostically challenging finding in prostate cancer (PCa) patients. This review aims to synthesize current evidence on PSMA-avid rib lesions in PCa and to propose a structured approach for differentiating true metastases from benign mimics. Methods: A comprehensive literature search across PubMed, EMBASE, Scopus, and Web of Science identified relevant studies on PSMA imaging interpretation, tracer-specific patterns, rib lesion morphology, and clinical correlates. Data on uptake intensity, CT features, lesion number, location, tracer type, patient-specific risk factors, and follow-up behavior were extracted and analyzed. Results: Most solitary rib lesions are benign, particularly in low-risk patients or when located in the anterior/lateral arcs. Metastatic lesions are more likely to present as multiple foci, show cortical destruction on CT, exhibit high uptake intensity, and occur in patients with elevated PSA, high Gleason score, or ongoing androgen deprivation. ¹⁸F-PSMA-1007 is especially prone to UBU in the ribs compared to ⁶⁸Ga-PSMA-11. Based on these variables, we propose a clinical decision tree to guide interpretation of PSMA-avid rib lesions. Conclusions: Accurate interpretation of rib lesions on PSMA PET/CT requires a multimodal, context-sensitive approach. Our diagnostic decision tree guides precise differentiation of benign versus metastatic rib lesions, enhancing staging accuracy and clinical decision-making. Biomarker-guided therapies offer potential for personalized treatment, though rib-specific validation remains a critical need. Full article

(This article belongs to the Special Issue Systematic Reviews and Meta-Analyses of Genitourinary Cancers (2nd Edition))

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15 pages, 253 KB

Open AccessArticle

Characteristics of Participants and Findings of the National Breast Cancer Early Detection Program in Saudi Arabia

by Fatina Al Tahan, Shaker A. Alomary, Hani Tamim, Mohammad Alkaiyat, Haifa Nassri, Khaled Alkattan and Abdul Rahman Jazieh

Cancers 2025, 17(21), 3403; https://doi.org/10.3390/cancers17213403 (registering DOI) - 22 Oct 2025

Abstract

Introduction: Breast cancer remains the most common cancer among women in Saudi Arabia and is often diagnosed at advanced stages due to delays in screening. This study aimed to examine the characteristics of women participating in a national breast cancer screening program, identify [...] Read more.

Introduction: Breast cancer remains the most common cancer among women in Saudi Arabia and is often diagnosed at advanced stages due to delays in screening. This study aimed to examine the characteristics of women participating in a national breast cancer screening program, identify the predictors of positive mammography findings, and assess the potential association between body mass index (BMI) and breast cancer risk. Methods: Data were obtained from the Saudi National Breast Cancer Early Detection Program that ran from May 2013 to July 2016. The study included Saudi women aged 30 years and older who underwent screening mammography and clinical breast examination. Demographic, clinical, and reproductive data were collected, and multivariable logistic regression analysis was used to determine the predictors of a positive mammogram and breast cancer diagnosis. Results: A total of 8348 women were screened (median age: 50 years), with 60 cases of breast cancer detected (detection rate: 7.4 per 1000). Most participants were either self-referred (62.4%) or referred by health educators (30.9), and 29.5% were illiterate. Oral contraceptive use was more common among women with breast cancer compared to those without (78.3% vs. 64.2%, p = 0.02), and the duration of use was significantly longer (median: 84 vs. 60 months, p = 0.041). However, in multivariable analysis, only abnormal findings on clinical breast examination were significantly associated with a positive mammogram (OR 21.3, 95% CI 7.9–57.1, p < 0.0001), but no independent association was found between BMI and breast cancer. Conclusions: The national screening program demonstrated a strong detection rate, with clinical breast examination being the only independent predictor of a positive mammogram. Larger studies including more breast cancer patients with longer follow-ups are needed to further investigate the influence of BMI and hormonal factors on breast cancer risk in Saudi women. Full article

(This article belongs to the Special Issue Cancer Screening and Primary Care)

20 pages, 597 KB

Open AccessReview

Proton Beam Therapy and the AYA Sarcoma Patient Journey: Highlighting Needs from Diagnosis to Survivorship

by Margaret M. Harris and Safia K. Ahmed

Cancers 2025, 17(21), 3402; https://doi.org/10.3390/cancers17213402 (registering DOI) - 22 Oct 2025

Abstract

Background: Adolescents and young adults (15–39 years of age at time of diagnosis: AYA) with sarcoma are a unique patient population. The objective of this review is to examine the literature outlining the benefits of proton beam therapy (PBT) for treatment of [...] Read more.

Background: Adolescents and young adults (15–39 years of age at time of diagnosis: AYA) with sarcoma are a unique patient population. The objective of this review is to examine the literature outlining the benefits of proton beam therapy (PBT) for treatment of AYA sarcoma patients, barriers to PBT, evaluation of AYA-specific considerations and challenges, and exploration of future opportunities for improvements in care. Methods: An electronic search was conducted using databases and online search engines, primarily PubMed. The search criteria included studies and reviews completed from 2015 to 2025. Results: 57 articles were reviewed and categorized into sections: PBT for the treatment of the AYA patient, barriers to PBT, AYA-specific considerations and challenges, and future directions for the care of an AYA patient. Conclusions: Through this review, PBT can be deemed necessary when treating AYA sarcoma patients with radiation therapy to decrease long-term therapy-related toxicities. Furthermore, considerations for caring for an AYA sarcoma patient must extend beyond evidence-based treatment plans and must embrace the patient as a whole person through acknowledgement of the challenging impact on physical, mental, and social well-being from symptoms to diagnosis, diagnosis to treatment, and treatment to survivorship. Full article

(This article belongs to the Special Issue Radiotherapy for Sarcoma)

17 pages, 2196 KB

Open AccessArticle

Diagnostic Models for Predicting Follicular Thyroid Carcinomas Using Circulating Plasma MicroRNAs

by Sin Woo Kang, Ji Min Kim, Sung-Chan Shin, Yong-Il Cheon, Bo Hyun Kim, Mijin Kim, Sang Soo Kim and Byung-Joo Lee

Cancers 2025, 17(21), 3401; https://doi.org/10.3390/cancers17213401 (registering DOI) - 22 Oct 2025

Abstract

Background: Follicular thyroid carcinoma (FC) accounts for 10–15% of all thyroid cancers. FC is challenging to diagnose using fine-needle aspiration (FNA), making diagnostic thyroidectomy the standard approach. Recent studies have explored the use of circulating microRNAs for thyroid cancer diagnosis. This study evaluated [...] Read more.

Background: Follicular thyroid carcinoma (FC) accounts for 10–15% of all thyroid cancers. FC is challenging to diagnose using fine-needle aspiration (FNA), making diagnostic thyroidectomy the standard approach. Recent studies have explored the use of circulating microRNAs for thyroid cancer diagnosis. This study evaluated the diagnostic value of circulating miRNAs in plasma for FC to potentially reduce unnecessary thyroidectomies and repeat invasive procedures. Methods: This study was a retrospective observational study, and included consecutively selected 90 patients who underwent thyroidectomy at Pusan National University Hospital between January 2013 and February 2024 and were diagnosed with FC (49 patients) or follicular thyroid adenoma (FA) (41 patients) on final histopathology. Of these, 58 patients were enrolled in the utility assessment and 32 patients were included in the validation test. Among the 58 patients included in the utility assessment, microarray analysis was conducted on 15 patients who were randomly selected to identify novel plasma miRNAs. Next, TaqMan qRT-PCR was performed to evaluate the diagnostic utility of five plasma miRNAs and to develop a predictive model capable of predicting FC from FA using logistic regression as the utility assessment on 58 patients. Finally, in the validation test, TaqMan qRT-PCR and statistical analysis were conducted again on 32 patients and the constructed predictive models, verifying the accuracy of the predictive model. Results: Using microarray analysis, a novel miRNA, miR-6085, was identified for its distinguishing capability between FC and FA. In the utility assessment, miR-6085, miR-146b-5p, miR-221, and miR-222 were significantly upregulated in the FC group. A predictive model combining these four miRNAs showed strong diagnostic value for FC, with an AUC of 0.928 (0.843, 1.000), sensitivity of 94.7% (84.2, 100), specificity of 86.4% (68.2, 100). The accuracy of this model was 76.2% (52.8, 91.8) in the validation test. Conclusions: A model combining four miRNAs (miR-6085, miR-146b-5p, miR-221, and miR-222) demonstrated high sensitivity, specificity, and accuracy, suggesting that it could be a useful tool for differentiating FC from FA. Full article

(This article belongs to the Section Cancer Biomarkers)

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13 pages, 481 KB

Open AccessArticle

Serum Iodine Levels and 8-Year Survival in Patients After Kidney Cancer Diagnosis

by Elżbieta Złowocka-Perłowska, Piotr Baszuk, Adam Kiljańczyk, Wojciech Marciniak, Róża Derkacz, Aleksandra Tołoczko-Grabarek, Andrzej Sikorski, Marcin Słojewski, Adam Gołąb, Artur Lemiński, Michał Soczawa, Magdalena Marciniak, Rodney J. Scott, Jacek Gronwald and Jan Lubiński

Cancers 2025, 17(21), 3400; https://doi.org/10.3390/cancers17213400 (registering DOI) - 22 Oct 2025

Abstract

Background/Objectives: The aim of this study was to evaluate the association between serum iodine (I) levels and kidney cancer mortality. The role of serum iodine levels in relation to 8-year survival rates in survivors of kidney cancer has not previously been established. In [...] Read more.

Background/Objectives: The aim of this study was to evaluate the association between serum iodine (I) levels and kidney cancer mortality. The role of serum iodine levels in relation to 8-year survival rates in survivors of kidney cancer has not previously been established. In this prospective study, we analyzed 284 consecutive, unselected survivors of kidney cancer and determined their 8-year survival in relation to iodine levels. Methods: Micronutrient levels were measured using inductively coupled plasma mass spectrometry (ICP-MS). Each survivors of kidney cancer was assigned to one of four groups based on the quartile distribution of iodine levels, ranked in ascending order. The multivariable models included covariates such as age at diagnosis, sex, smoking status, type of surgery, histopathological classification and serum levels of selenium, zinc, copper and the zinc-to-copper ratio. Results: We observed that survivors of kidney cancer with serum iodine levels in quartiles III and IV had significantly higher all-cause mortality compared to those in quartile II (reference quartile) (HR = 2.83; p = 0.012; HR = 2.64; p = 0.017). Furthermore, multivariable analysis revealed a significant association between serum iodine levels (quartiles III and IV vs. quartile II) and mortality due to kidney cancer progression (HR = 4.17; p = 0.031; HR = 3.94; p = 0.038, respectively). This association was significant only among men in quartile IV (HR = 16.5; p = 0.027). Additionally a positive association was observed between iodine levels in quartile IV and all-cause mortality from non–kidney cancer–related deaths (HR = 5.41; p = 0.05). Conclusions: To our knowledge, this study is the first investigation of relationship between serum iodine levels and survival of survivors of kidney cancer. Full article

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

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16 pages, 6261 KB

Open AccessArticle

Spatial Organisation and Invasive Behaviour of Metastatic Cutaneous Squamous Cell Carcinoma-Derived Multicellular Spheroids Reflect Tumour Cell Phenotype

by Benjamin Genenger, Jessica Conley, Chelsea Penney, Luke McAlary, Jay R. Perry, Bruce Ashford and Marie Ranson

Cancers 2025, 17(21), 3399; https://doi.org/10.3390/cancers17213399 (registering DOI) - 22 Oct 2025

Abstract

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) is a very common skin malignancy of the head and neck area, with a propensity to spread to local lymph nodes. Epithelial-to-mesenchymal transition (EMT) and cancer-associated fibroblasts (CAFs) play a well-documented role in the progression of [...] Read more.

Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) is a very common skin malignancy of the head and neck area, with a propensity to spread to local lymph nodes. Epithelial-to-mesenchymal transition (EMT) and cancer-associated fibroblasts (CAFs) play a well-documented role in the progression of the disease. In this study, we developed and characterised multicellular tumour spheroids (MCTS) composed of patient-derived metastatic cSCC cell lines—each exhibiting distinct phenotypes—combined with either dermal- or lymph node-derived fibroblasts. We aimed to investigate how these cellular combinations influence MCTS formation, spatial architecture, and invasive behaviour. We hypothesised that the interplay between different cSCC and fibroblast cell combinations would differentially influence spheroid formation and invasion. Methods: Using live-cell microscopy we assessed the spatial architectures specific to each cell line-fibroblast combination and evaluated the expression of EMT and CAF markers. Furthermore, we utilised MCTS in invasion models to investigate associations between the mode of invasion and the EMT phenotype of the cancer cell line. Results: We show that metastatic cSCC/fibroblast MCTS self-organise into distinct spatial architectures. They also invade through collagen in a manner influenced by fibroblasts but dominated by the EMT status of the originating cancer cells. Conclusions: These findings highlight the physiological relevance and utility of MCTS as models for investigating tumour–stroma interactions and invasion dynamics in metastatic cSCC. Full article

(This article belongs to the Special Issue Multicellular 3D Models of Cancer)

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11 pages, 829 KB

Open AccessArticle

Artificial Intelligence for Lymph Node Detection and Malignancy Prediction in Endoscopic Ultrasound: A Multicenter Study

by Belén Agudo Castillo, Miguel Mascarenhas Saraiva, António Miguel Martins Pinto da Costa, João Ferreira, Miguel Martins, Francisco Mendes, Pedro Cardoso, Joana Mota, Maria João Almeida, João Afonso, Tiago Ribeiro, Marcos Eduardo Lera dos Santos, Matheus de Carvalho, María Morís, Ana García García de Paredes, Daniel de la Iglesia García, Carlos Estebam Fernández-Zarza, Ana Pérez González, Khoon-Sheng Kok, Jessica Widmer, Uzma D. Siddiqui, Grace E. Kim, Susana Lopes, Pedro Moutinho Ribeiro, Filipe Vilas-Boas, Eduardo Hourneaux de Moura, Guilherme Macedo and Mariano González-Haba Ruiz Show full author list Hide full author list

Cancers 2025, 17(21), 3398; https://doi.org/10.3390/cancers17213398 - 22 Oct 2025

Abstract

Background/Objectives: Endoscopic ultrasound (EUS) is crucial for lymph node (LN) characterization, playing a key role in oncological staging and treatment guidance. EUS criteria for predicting malignancy are imprecise, and histologic diagnosis may have limitations. This multicenter study aimed to evaluate the effectiveness [...] Read more.

Background/Objectives: Endoscopic ultrasound (EUS) is crucial for lymph node (LN) characterization, playing a key role in oncological staging and treatment guidance. EUS criteria for predicting malignancy are imprecise, and histologic diagnosis may have limitations. This multicenter study aimed to evaluate the effectiveness of a novel artificial intelligence (AI)–based system in predicting LN malignancy from EUS images. Methods: This multicenter study included EUS images from nine centers. Lesions were labeled (“malignant” or “benign”) and delimited with bounding boxes. Definitive diagnoses were based on cytology/biopsy or surgical specimens and, if negative, a minimum six-month clinical follow-up. A convolutional neural network (CNN) was developed using the YOLO (You Only Look Once) architecture, incorporating both detection and classification modules. Results: A total of 59,992 images from 82 EUS procedures were analyzed. The CNN distinguished malignant from benign lymph nodes with a sensitivity of 98.8% (95% CI: 98.5–99.2%), specificity of 99.0% (95% CI: 98.3–99.7%), and precision of 99.0% (95% CI: 98.4–99.7%). The negative and positive predictive values for malignancy were 98.8% and 99.0%, respectively. Overall diagnostic accuracy was 98.3% (95% CI: 97.6–99.1%). Conclusions: This is the first study evaluating the performance of deep learning systems for LN assessment using EUS imaging. Our AI-powered imaging model shows excellent detection and classification capabilities, emphasizing its potential to provide a valuable tool to refine LN evaluation with EUS, ultimately supporting more tailored, efficient patient care. Full article

(This article belongs to the Special Issue Application of Artificial Intelligence-Based Approaches in Cancer Diagnosis, Treatment and Prognosis)

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18 pages, 1088 KB

Open AccessReview

Challenges in the Evolving Role of Calreticulin as a Promising Target for Precision Medicine in Myeloproliferative Neoplasms

by Alessandro Costa and Massimo Breccia

Cancers 2025, 17(21), 3397; https://doi.org/10.3390/cancers17213397 (registering DOI) - 22 Oct 2025

Abstract

More than a decade after its discovery, advances have been made in understanding the oncogenic role of mutant CALR in BCR::ABL1-negative myeloproliferative neoplasms (MPNs). Disease biology has proven to be distinct from other MPN subtypes, with meaningful differences that have created opportunities [...] Read more.

More than a decade after its discovery, advances have been made in understanding the oncogenic role of mutant CALR in BCR::ABL1-negative myeloproliferative neoplasms (MPNs). Disease biology has proven to be distinct from other MPN subtypes, with meaningful differences that have created opportunities for therapeutic targeting of CALR-mutant clones. Among the approaches under investigation, immunotherapy has advanced furthest into clinical development and holds promise. Several strategies are now being explored, including monoclonal antibodies directed against the CALR neoepitope, T-cell–redirecting bispecific antibodies, precision antibody–drug conjugates, vaccination approaches, and CAR T-cell therapies. Early-phase clinical trials with fully human anti-CALR monoclonal antibodies (e.g., INCA033989) have shown very promising hematologic and molecular responses with manageable toxicity. In preclinical models, bispecific antibodies and CAR T-cell therapy offer additional avenues to exploit the selective cell-surface localization of mutant CALR. By contrast, vaccination strategies have so far demonstrated limited clinical efficacy, and their potential in clinical practice remains challenging. At the same time, the complexity of CALR-driven disease raises key questions, including whether anti-CALR therapies can shift treatment goals beyond thrombotic risk reduction, how best to monitor clonal burden, and how to address immune escape. In this review, we highlight the latest therapeutic advances in CALR-mutated MPNs while outlining the critical unmet needs that will shape the future of care for these patients. Full article

(This article belongs to the Special Issue Insights from the Editorial Board Member)

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27 pages, 1843 KB

Open AccessArticle

Oncological Outcomes of De-Escalation of Axillary Surgery in Breast Cancer Patients at a Referral Cancer Center in Colombia

by Sandra Esperanza Díaz-Casas, Andres Augusto Reyes-Agudelo, Oscar Alberto Vergara-Gamarra, Ximena Briceño-Morales, Luis Guzmán-AbiSaab, Daniel Contreras-Perez, Carlos Lehmann-Mosquera, Javier Ángel-Aristizábal, Mauricio García-Mora, Carlos Duarte-Torres, Iván Mariño-Lozano, Raúl Suárez-Rodríguez and Marcela Núñez-Lemus

Cancers 2025, 17(21), 3396; https://doi.org/10.3390/cancers17213396 - 22 Oct 2025

Abstract

Background/Objectives: De-escalation of axillary surgery with sentinel lymph node biopsy (SLNB) has been shown to decrease morbidity in breast cancer patients without affecting oncological outcomes. However, there are very few reports on its applicability in real-world clinical practice, especially in middle-income countries. [...] Read more.

Background/Objectives: De-escalation of axillary surgery with sentinel lymph node biopsy (SLNB) has been shown to decrease morbidity in breast cancer patients without affecting oncological outcomes. However, there are very few reports on its applicability in real-world clinical practice, especially in middle-income countries. Methods: A retrospective historical cohort study was conducted, including 787 patients with clinical stage I–IIIA breast cancer treated from 2013 to 2023 at the INC in Colombia. Two groups were analyzed based on the timing of the axillary procedure: patients undergoing SLNB as initial surgery (Upfront SLNB) and those receiving neoadjuvant chemotherapy (Post-NACT SLNB). Results: The overall sentinel lymph node (SLN) identification rate was 99.3%. SLN positivity was 32% in Upfront SLNB and 13.1% in Post-NACT SLNB. Axillary lymph node dissection (ALND) was omitted in 56% of patients with node-positive Upfront SLNB; it was avoided in 86.8% of the Post-NACT group with complete axillary response (ypN0). Regional recurrence rates were 2.33%. In multivariate analysis, the main factors linked to recurrence and mortality were triple-negative and luminal B HER2-negative biological subtypes, histological grade 2, and tumor size ≥ 2 cm. At 60 months of follow-up, 91.4% (95% CI: 88.9–93.9) of patients remained recurrence-free (time-recurrence (TR)), and overall survival (OS) was 96.1% (95% CI: 94.5–97.7), with no differences observed based on the axillary surgical strategy. Conclusions: Sentinel lymph node biopsy (SLNB) is an oncologically safe procedure for patients with early-stage and locally advanced breast cancer with an adequate response to neoadjuvant systemic treatment. Full article

(This article belongs to the Section Cancer Therapy)

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13 pages, 1190 KB

Open AccessArticle

Carbon Ion Radiotherapy for Retroperitoneal Sarcoma: A Single-Institution Study

by Reiko Imai, Tsukasa Yonemoto, Nobuhito Araki, Hirotoshi Takiyama, Hiroaki Ikawa, Shigeru Yamada and Hitoshi Ishikawa

Cancers 2025, 17(20), 3395; https://doi.org/10.3390/cancers17203395 (registering DOI) - 21 Oct 2025

Abstract

Background/Objectives: Surgery remains the mainstay of treatment for retroperitoneal sarcoma (RPS); however, definitive therapeutic strategies for patients with insufficient surgical margins and unresectable disease owing to locally advanced RPS remain unclear. Carbon ion radiotherapy (CIRT) has been employed in patients with unresectable RPS. [...] Read more.

Background/Objectives: Surgery remains the mainstay of treatment for retroperitoneal sarcoma (RPS); however, definitive therapeutic strategies for patients with insufficient surgical margins and unresectable disease owing to locally advanced RPS remain unclear. Carbon ion radiotherapy (CIRT) has been employed in patients with unresectable RPS. This study aimed to evaluate the effectiveness of CIRT in this patient population. Methods: A retrospective analysis was conducted in 76 patients with unresectable RPS treated with CIRT. Of these, 95% had a confirmed prognosis until 2022. In 74 patients, the prescribed relative biological effectiveness dose was 70.4 Gy, delivered in 16 fractions over 4 weeks. Respiratory gating was used, and spot scanning irradiation has been performed in all patients since 2016. Results: The 3- and 5-year overall survival rates for the entire cohort were 68.3% and 49.4%, respectively, with a median overall survival time of 58.1 months. The 3- and 5-year local control rates were 79.0% and 72.0%, respectively. Among 47 naïve patients with treatment-naïve tumors, the 3- and 5-year abdominal recurrence-free survival rates were 51.1% and 29.1%, respectively. Late adverse events of grade 3 or higher occurred in 4 (5.2%) patients. Conclusions: CIRT represents a definitive treatment option for patients with unresectable RPS. In the future, multicenter studies should be conducted to evaluate the effectiveness of CIRT for RPS in larger patient cohorts. Full article

(This article belongs to the Special Issue Radiotherapy for Sarcoma)

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18 pages, 2025 KB

Open AccessArticle

A Priori Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer Using Deep Features from Pre-Treatment MRI and CT

by Deok Hyun Jang, Laurentius O. Osapoetra, Lakshmanan Sannachi, Belinda Curpen, Ana Pejović-Milić and Gregory J. Czarnota

Cancers 2025, 17(20), 3394; https://doi.org/10.3390/cancers17203394 - 21 Oct 2025

Abstract

Background: Response to neoadjuvant chemotherapy (NAC) is a key prognostic indicator in breast cancer, yet current assessment relies on postoperative pathology. This study investigated the use of deep features derived from pre-treatment MRI and CT scans, in conjunction with clinical variables, to [...] Read more.

Background: Response to neoadjuvant chemotherapy (NAC) is a key prognostic indicator in breast cancer, yet current assessment relies on postoperative pathology. This study investigated the use of deep features derived from pre-treatment MRI and CT scans, in conjunction with clinical variables, to predict treatment response a priori. Methods: Two response endpoints were analyzed: pathologic complete response (pCR) versus non-pCR, and responders versus non-responders, with response defined as a reduction in tumor size of at least 30%. Intratumoral and peritumoral segmentations were generated on contrast-enhanced T1-weighted (CE-T1) and T2-weighted MRI, as well as contrast-enhanced CT images of tumors. Deep features were extracted from these regions using ResNet10, ResNet18, ResNet34, and ResNet50 architectures pre-trained with MedicalNet. Handcrafted radiomic features were also extracted for comparison. Feature selection was conducted with minimum redundancy maximum relevance (mRMR) followed by recursive feature elimination (RFE), and classification was performed using XGBoost across ten independent data partitions. Results: A total of 177 patients were analyzed in this study. ResNet34-derived features achieved the highest overall classification performance under both criteria, outperforming handcrafted features and deep features from other ResNet architectures. For distinguishing pCR from non-pCR, ResNet34 achieved a balanced accuracy of 81.6%, whereas handcrafted radiomics achieved 77.9%. For distinguishing responders from non-responders, ResNet34 achieved a balanced accuracy of 73.5%, compared with 70.2% for handcrafted radiomics. Conclusions: Deep features extracted from routinely acquired MRI and CT, when combined with clinical information, improve the prediction of NAC response in breast cancer. This multimodal framework demonstrates the value of deep learning-based approaches as a complement to handcrafted radiomics and provides a basis for more individualized treatment strategies. Full article

(This article belongs to the Special Issue CT/MRI/PET in Cancer)

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15 pages, 1175 KB

Open AccessArticle

The Impact of Local Ablative Therapies as Bridging Treatment on Overall Survival Following Liver Transplantation in Patients with HCC

by Laura Schwenk, Felix Dondorf, Oliver Rohland, Aladdin Ali-Deeb, Utz Settmacher and Falk Rauchfuß

Cancers 2025, 17(20), 3393; https://doi.org/10.3390/cancers17203393 - 21 Oct 2025

Abstract

Background: The use of neoadjuvant therapies in patients with hepatocellular carcinoma prior to liver transplantation has gained increasing popularity in recent years. To date, there are only limited data investigating the impact of neoadjuvant therapy on post-transplant survival. Methods: In this retrospective study, [...] Read more.

Background: The use of neoadjuvant therapies in patients with hepatocellular carcinoma prior to liver transplantation has gained increasing popularity in recent years. To date, there are only limited data investigating the impact of neoadjuvant therapy on post-transplant survival. Methods: In this retrospective study, we evaluated patients with hepatocellular carcinoma who underwent deceased donor or living donor liver transplantation at Jena University Hospital between 2019 and 2023. Comprehensive clinical and pathological variables were systematically analyzed, including correlations between neoadjuvant therapy use, tumor burden and overall survival. Survival outcomes were estimated using the Kaplan–Meier method. Results: A total of 107 patients were included in the analysis, of whom 90 received neoadjuvant therapy prior to transplantation. Treatment modalities comprised SIRT, TACE, liver resection and combined SIRT and TACE. The 1-, 3-, and 5-year OS rates following transplantation were 93.5%, 82.2%, and 79.4%, respectively. Recurrence-free survival at 1, 3, and 5 years was 91.6%, 85.0%, and 83.2%, respectively. Among the various neoadjuvant strategies, SIRT and TACE yielded the highest OS rates. Patients listed outside the transplantation criteria (Milan, UCSF, up-to-seven) at the time of initial diagnosis who underwent SIRT had significantly better OS than those outside the criteria who underwent TACE. In contrast, among patients within the Milan, UCSF and up-to-seven criteria, TACE was associated with superior OS compared with SIRT. Conclusion: The use of neoadjuvant therapies confers a significant survival benefit following liver transplantation in patients with HCC. TACE appears to be most suitable for patients listed within established transplantation criteria, who consequently have a lower tumor burden. In contrast, SIRT is more beneficial for patients with a higher tumor burden and those beyond standard transplantation criteria. A limitation of our study, however, is that the included SIRT cohort comprised only 24 patients, and TACE was preferentially performed in patients with a lower tumor burden, which means that a selection bias cannot be fully excluded. Overall, further studies are required to define the optimal bridging strategies. Full article

(This article belongs to the Special Issue Surgical Treatment of Hepatocellular Carcinoma)

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10 pages, 664 KB

Open AccessReview

The Central Anatomical Question: Treatment of Lymphoma Within Border-Zone Anatomical Sites Adjacent to the Central Nervous System

by Candace Marsters, Chai Phua, Maria MacDonald, Gabriel Boldt and Seth Climans

Cancers 2025, 17(20), 3392; https://doi.org/10.3390/cancers17203392 - 21 Oct 2025

Abstract

Lymphomas involving the central nervous system (CNS) have worse outcomes, including both primary and secondary CNS lymphomas, which are associated with poorer overall survival outcomes. The World Health Organization classifies CNS lymphoma as arising from the brain, leptomeninges, and spinal cord, but this [...] Read more.

Lymphomas involving the central nervous system (CNS) have worse outcomes, including both primary and secondary CNS lymphomas, which are associated with poorer overall survival outcomes. The World Health Organization classifies CNS lymphoma as arising from the brain, leptomeninges, and spinal cord, but this simplified CNS anatomical definition fails to incorporate areas of ambiguity that can be clinically relevant for treatment decision making. In this article, we review the anatomical boundaries of CNS lymphoma within select border-zone biological structures located at the CNS borders in order to gain a consensus working definition of CNS disease boundaries. We review anatomical localizations with border-zone CNS boundaries, including the dura, cavernous sinus, circumventricular organs, pituitary gland, and cranial nerves. Though some portions of the eye would be considered CNS and others extra-CNS, recommendations for this structure are outside the scope of this review. Through this review, we examine the impact of lymphomatous invasion on select CNS-bordering anatomical structures, aiming to better define treatment categorization as CNS or extra-CNS, with a focus on B cell lymphoma types. Full article

(This article belongs to the Special Issue Primary Central Nervous System Lymphoma: A Challenging Disease)

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15 pages, 354 KB

Open AccessArticle

The Effectiveness of ¡Salud!, por la Vida, an Educational Intervention to Increase Colorectal Cancer Screening in Puerto Rico

by Josheili Llavona-Ortiz, Maria E. Fernández, Ileska M. Valencia-Torres, Francisco J. Muñoz-Torres, Marievelisse Soto-Salgado, Yara Sánchez-Cabrera and Vivian Colón-López

Cancers 2025, 17(20), 3391; https://doi.org/10.3390/cancers17203391 - 21 Oct 2025

Abstract

Background/Objectives: Colorectal cancer (CRC) is the leading cancer-related death in Puerto Rico (PR). Yet CRC screening (CRCS) rates remain low. We developed ¡Salud!, por la Vida, an educational intervention aiming to increase CRCS among age-eligible adults living in PR. Methods: [...] Read more.

Background/Objectives: Colorectal cancer (CRC) is the leading cancer-related death in Puerto Rico (PR). Yet CRC screening (CRCS) rates remain low. We developed ¡Salud!, por la Vida, an educational intervention aiming to increase CRCS among age-eligible adults living in PR. Methods: We conducted a cluster randomized controlled trial among adults 50–75 years old at Federally Qualified Health Clinics in PR. Participants could not have a history of CRC nor be currently adherent to CRCS guidelines for a fecal occult blood test (FOBT) or fecal immunochemical test (FIT) (within last year) or colonoscopy (within last 5–10 years). Out of 445 randomized participants, 355 completed the study procedures (Control: 277; Intervention: 78) and were included in the main analysis. Participants in the intervention arm completed baseline and follow-up questionnaires alongside the educational intervention (at baseline) and two reminder calls (before follow-up) within a four-month period. Control arm participants only completed baseline and follow-up questionnaires within the same period. All participants were followed up to assess CRCS completion. Results: Post-trial screening rates were significantly higher in the intervention group: FOBT/FIT (55% vs. 39%, p = 0.02), colonoscopy (10% vs. 3%, p = 0.02), and any CRCS (60% vs. 41%, p < 0.01). Compared to controls, those in the intervention group showed a 48% higher probability of undergoing any CRCS (RR = 1.48, 95%CI: 1.17, 1.86), were 1.4 times more likely to complete a FOBT/FIT (RR = 1.40, 95%CI: 1.09, 1.80), and were over 3 times more likely to undergo a colonoscopy (RR = 3.16, 95%CI: 1.26, 7.91). Conclusions: The findings underscore the efficacy of the intervention in increasing CRCS uptake, potentially preventing late-stage detection and reducing CRC mortality in PR. Full article

(This article belongs to the Special Issue Cancer Screening and Primary Care)

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10 pages, 621 KB

Open AccessArticle

Evaluation of a Novel Tapered Tip EUS-FNB Needle: A UK Multicentre Study

by Darragh Storan, John Leeds, Arif Hussenbux, Mohamed Elseragy, Ruridh Allen, Tareq El Menabawey, Aaron McGowan, Matthew T. Huggett, Umair Kamran, Bidour Awadelkarim, Beate Haugk, Kofi Oppong and Manu Nayar

Cancers 2025, 17(20), 3390; https://doi.org/10.3390/cancers17203390 - 21 Oct 2025

Abstract

Introduction: A new core biopsy needle with a novel tapered stylet tip has been introduced for endoscopic ultrasound-guided fine needle biopsy (EUS-FNB). The tapered point stylet is purported to improve ease of puncture, leading to improved tissue acquisition and accuracy. However, there [...] Read more.

Introduction: A new core biopsy needle with a novel tapered stylet tip has been introduced for endoscopic ultrasound-guided fine needle biopsy (EUS-FNB). The tapered point stylet is purported to improve ease of puncture, leading to improved tissue acquisition and accuracy. However, there are no data available in the published literature. The aim of this study was to compare the diagnostic performance of the tapered stylet needle with conventional end-cutting FNB needles for tissue acquisition from solid lesions. Methods: Patients who underwent EUS-FNB of a solid lesion using the tapered stylet FNB needle across four tertiary hepatopancreaticobiliary centres in the UK were included in the study. Demographic, clinical, and performance outcomes were included in the analysis. Diagnostic performance was compared with a similar cohort of patients who underwent EUS-FNB using standard end-cutting FNB needles with a blunt-tipped stylet. The primary outcome was accuracy for the diagnosis of malignancy. Results: A total of 270 patients were included for analysis; 129 patients (48%) had sampling with the novel tapered stylet tip needle, among which 50% were female, the median age was 69, 74% had pancreatic lesions, and 80% had a final diagnosis of malignancy; 141 control cases (52%) were included for comparison, among which 48% were female, the median age was 68, 67% had pancreatic lesions, and 72% had a final diagnosis of malignancy. The tapered stylet needle demonstrated a sensitivity of 90% and an NPV of 72% for the diagnosis of malignancy compared with 88% and 77% for controls (p = 0.147). The overall diagnostic accuracy of the tapered stylet needle was 92.2% compared with 91.5% for controls (p = 0.634). Conclusions: The novel tapered tip stylet FNB needle demonstrated comparable sensitivity, NPV, and diagnostic accuracy to conventional FNB needles. This is the first and largest study reporting results for this new needle. However, further large comparative studies are warranted to validate our results and to determine if the tapered stylet offers an advantage over the conventional design. Full article

(This article belongs to the Special Issue New Advances in Oncology Research and Practice)

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18 pages, 4021 KB

Open AccessArticle

A Novel Allosteric Inhibitor Targeting IMPDH at Y233 Overcomes Resistance to Tyrosine Kinase Inhibitors in Lymphoma

by Nagarajan Pattabiraman, Cosimo Lobello, David Rushmore, Luca Mologni, Mariusz Wasik and Johnvesly Basappa

Cancers 2025, 17(20), 3389; https://doi.org/10.3390/cancers17203389 - 21 Oct 2025

Abstract

Background/Objective: Oncogenic tyrosine kinases (TKs) such as ALK and SRC promote cancer progression, but their effects on metabolic enzymes are still not well understood. This study examines how TK signaling regulates inosine monophosphate dehydrogenase 2 (IMPDH2), a rate-limiting enzyme in purine biosynthesis, and [...] Read more.

Background/Objective: Oncogenic tyrosine kinases (TKs) such as ALK and SRC promote cancer progression, but their effects on metabolic enzymes are still not well understood. This study examines how TK signaling regulates inosine monophosphate dehydrogenase 2 (IMPDH2), a rate-limiting enzyme in purine biosynthesis, and assesses its potential as a therapeutic target. Methods: Phosphoproteomic screening and in vitro kinase assays were used to identify phosphorylation sites on IMPDH2. Lipid-binding assays explored the role of phosphatidylinositol 3-phosphate (PI3P) in IMPDH2 regulation. Structure-based virtual screening discovered small-molecule allosteric inhibitors, which were tested in lymphoma cell models, including ALK and BTK-inhibitor resistant lines. Results: Here, we identify Inosine monophosphate dehydrogenase-2 (IMPDH2), a rate-limiting enzyme in purine biosynthesis, as a novel substrate of ALK and SRC. We show that phosphorylation at the conserved Y233 residue within the allosteric domain enhances IMPDH2 activity, linking TK signaling to metabolic reprogramming in cancer cells. We further identify PI3P as a natural lipid inhibitor that binds IMPDH2 and suppresses its enzymatic function. Using structure-based virtual screening, we developed Comp-10, a first-in-class allosteric IMPDH inhibitor. Unlike classical active-site inhibitors such as mycophenolic acid (MPA), Comp-10 decreases IMPDH1/2 protein levels, blocks filament (rod/ring) formation, and inhibits the growth of ALK and BTK inhibitor-resistant lymphoma cells. Comp-10 acts post-transcriptionally and avoids compensatory IMPDH upregulation observed with MPA (rod/ring) formation, and inhibited growth in TKI-resistant lymphoma cells. Notably, Comp-10 avoided the compensatory IMPDH upregulation observed with MPA. Conclusion: These findings uncover a novel TK–IMPDH2 signaling axis and provide mechanistic and therapeutic insight into the allosteric regulation of IMPDH2. Comp-10 represents a promising therapeutic candidate for targeting metabolic vulnerabilities in tyrosine kinase driven cancers. Full article

(This article belongs to the Section Molecular Cancer Biology)

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19 pages, 8646 KB

Open AccessArticle

Impact of Diagnostic Confidence, Perceived Difficulty, and Clinical Experience in Facial Melanoma Detection: Results from a European Multicentric Teledermoscopic Study

by Alessandra Cartocci, Alessio Luschi, Sofia Lo Conte, Elisa Cinotti, Francesca Farnetani, Aimilios Lallas, John Paoli, Caterina Longo, Elvira Moscarella, Danica Tiodorovic, Ignazio Stanganelli, Mariano Suppa, Emi Dika, Iris Zalaudek, Maria Antonietta Pizzichetta, Jean Luc Perrot, Imma Savarese, Magdalena Żychowska, Giovanni Rubegni, Mario Fruschelli, Ernesto Iadanza, Gabriele Cevenini and Linda Tognetti Show full author list Hide full author list

Cancers 2025, 17(20), 3388; https://doi.org/10.3390/cancers17203388 - 21 Oct 2025

Abstract

Background: Diagnosing facial melanoma, specifically lentigo maligna (LM) and lentigo maligna melanoma (LMM), is a daily clinical challenge, particularly for small or traumatized lesions. LM and LMM are part of the broader group of atypical pigmented facial lesions (aPFLs), which also includes benign [...] Read more.

Background: Diagnosing facial melanoma, specifically lentigo maligna (LM) and lentigo maligna melanoma (LMM), is a daily clinical challenge, particularly for small or traumatized lesions. LM and LMM are part of the broader group of atypical pigmented facial lesions (aPFLs), which also includes benign look-alikes such as solar lentigo (SL), atypical nevi (AN), seborrheic keratosis (SK), and seborrheic-lichenoid keratosis (SLK), as well as pigmented actinic keratosis (PAK), a potentially premalignant keratinocytic lesion. Standard dermoscopy with handheld devices is the most widely used diagnostic tool in dermatology, but its accuracy heavily depends on the clinician’s experience and the perceived difficulty of the case. As a result, many benign aPFLs are excised for histological analysis, often leading to aesthetic concerns. Reflectance confocal microscopy (RCM) can reduce the need for biopsies, but it is limited to specialized centers and requires skilled operators. Aims: This study aimed to assess the impact of personal skill, diagnostic confidence, and perceived difficulty on the diagnostic accuracy and management in the differential dermoscopic diagnosis of aPFLs. Methods: A total of 1197 aPFLs dermoscopic images were examined on a teledermoscopic web platform by 155 dermatologists and residents with 4 skill levels (<1, 1–4, 5–8, >8 years). They were asked to give a diagnosis, to estimate their confidence and rate the case, and choose a management strategy: “follow-up”, “RCM” or “biopsy”. Diagnostic accuracy was examined according to the personal skill level, confidence level, and rating in three settings: (I) all seven diagnoses, (II) LM vs. PAK vs. fully benign aPFLs, (III) malignant vs benign aPFLs. The same analyses were performed for management decisions. Results: The diagnostic confidence has a certain impact on the diagnostic accuracy, both in terms of multi-class diagnosis of six aPFLs in diagnostic (setting 1) and in benign vs malignant (setting 3) or benign vs. malignant/premalignant discrimination (setting 2). The perceived difficulty influences the management of benign lesions, with easy ratings predominantly matching with “follow-up” decision in benign cases, but not that of malignant lesions assigned to “biopsy”. The experience level had an impact on the perception of the number of real easy cases and had no to minimal impact on the average diagnostic accuracy of aPFLs. It, however, has an impact on the management strategy and specifically in terms of error reduction, namely the lowest rates of missed malignant cases after 8 years of experience and the lowest rates of inappropriate biopsies of benign lesions after 1 year of experience. Conclusions: The noninvasive diagnosis and management of aPFLs rest on a daily challenge. Highlighting which specific subgroups of lesions need attention and second-level examination (RCM) or biopsy can help detect early malignant cases, and, in parallel, reduce the rate of unnecessary removal of benign lesions. Full article

(This article belongs to the Special Issue Advances in Skin Cancer: Diagnosis, Treatment and Prognosis)

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26 pages, 1154 KB

Open AccessReview

AI-Based Characterization of Breast Cancer in Mammography and Tomosynthesis: A Review of Radiomics and Deep Learning for Subtyping, Staging, and Prognosis

by Ana M. Mota

Cancers 2025, 17(20), 3387; https://doi.org/10.3390/cancers17203387 - 21 Oct 2025

Abstract

Background: Biopsy remains the gold standard for characterizing breast cancer, but it is invasive, costly, and may not fully capture tumor heterogeneity. Advances in artificial intelligence (AI) now allow for the extraction of biological and clinical information from medical images, raising the [...] Read more.

Background: Biopsy remains the gold standard for characterizing breast cancer, but it is invasive, costly, and may not fully capture tumor heterogeneity. Advances in artificial intelligence (AI) now allow for the extraction of biological and clinical information from medical images, raising the possibility of using imaging as a non-invasive alternative. Methods: A semi-systematic review was conducted to identify AI-based approaches applied to mammography (MM) and breast tomosynthesis (BT) for tumor subtyping, staging, and prognosis. A PubMed search retrieved 1091 articles, of which 81 studies met inclusion criteria (63 MM, 18 BT). Studies were analyzed by clinical target, modality, AI pipeline, number of cases, dataset type, and performance metrics (AUC, accuracy, or C-index). Results: Most studies focused on tumor subtyping, particularly receptor status and molecular classification. Contrast-enhanced spectral mammography (CESM) was frequently used in radiomics pipelines, while end-to-end deep learning (DL) approaches were increasingly applied to MM. Deep models achieved strong performance for ER/PR and HER2 status prediction, especially in large datasets. Fewer studies addressed staging or prognosis, but promising results were obtained for axillary lymph node (ALN) metastasis and pathological complete response (pCR). Multimodal and longitudinal approaches—especially those combining MM or BT with MRI or ultrasound—show improved accuracy but remain rare. Public datasets were used in only a minority of studies, limiting reproducibility. Conclusions: AI models can predict key tumor characteristics directly from MM and BT, showing promise as non-invasive tools to complement or even replace biopsy. However, challenges remain in terms of generalizability, external validation, and clinical integration. Future work should prioritize standardized annotations, larger multicentric datasets, and integration of histological or transcriptomic validation to ensure robustness and real-world applicability. Full article

(This article belongs to the Special Issue Advances in Breast Cancer Imaging: From Detection to Personalized Diagnosis)

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26 pages, 2438 KB

Open AccessReview

Exosomes in HPV-Associated Cancers: From Biomarkers to Engineered Therapeutics

by Muharrem Okan Cakir, Melis Selek, Betul Yilmaz, Mustafa Ozdogan and G. Hossein Ashrafi

Cancers 2025, 17(20), 3386; https://doi.org/10.3390/cancers17203386 - 21 Oct 2025

Abstract

Background/Objectives: Human papillomavirus (HPV) is the main causative agent of cervical cancer and contributes to a significant proportion of other anogenital and oropharyngeal malignancies. The need for better biomarkers and therapeutic approaches in HPV-associated cancers has drawn attention to exosomes, small extracellular vesicles [...] Read more.

Background/Objectives: Human papillomavirus (HPV) is the main causative agent of cervical cancer and contributes to a significant proportion of other anogenital and oropharyngeal malignancies. The need for better biomarkers and therapeutic approaches in HPV-associated cancers has drawn attention to exosomes, small extracellular vesicles known for their stability, biomolecule transport capabilities, and role in cell-to-cell communication. Methods: This review comprehensively evaluates recent literature on the diagnostic, prognostic, and therapeutic applications of small extracellular vesicles, particularly exosomes, in HPV-related cancers. It analyzes findings on exosomal nucleic acids, proteins, and long non-coding RNAs, as well as engineered exosome-based therapies. Results: Exosomal miRNAs (e.g., miR-204-5p, miR-99a-5p, miR-21), proteins (e.g., glycolytic enzymes, HSP90), and lncRNAs (e.g., HOTAIR, DLEU1) have emerged as promising biomarkers for disease detection and monitoring. Exosomal cargo actively participates in HPV-related tumor progression. For example, miRNAs such as miR-21 and miR-146a modulate immune cell polarization and inflammatory signaling, while lncRNAs like HOTAIR promote oncogenic transcriptional programs. Exosomal proteins including HSP90 and ANXA1 facilitate extracellular matrix remodeling and immune evasion, thereby influencing tumor growth and metastasis. In HPV-positive head and neck and cervical cancers, exosomal cargo reflects HPV status, tumor progression, and treatment response. Therapeutic studies demonstrate the utility of exosomes in vaccine delivery, immune modulation, and drug delivery systems, including the use of PROTACs. However, clinical translation faces barriers including isolation protocol standardization, biomarker validation, and scalable production. Conclusions: Exosomes hold great promise for integration into diagnostic and therapeutic workflows for HPV-related cancers. Future research should focus on resolving standardization issues, validating biomarkers in diverse cohorts, and optimizing engineered exosome platforms for targeted therapy. Full article

(This article belongs to the Collection The Development of Anti-cancer Agents)

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