Journal Description
Cancers
Cancers
is a peer-reviewed, open access journal of oncology, published semimonthly online by MDPI. The Irish Association for Cancer Research (IACR), Spanish Association for Cancer Research (ASEICA), Biomedical Research Centre (CIBM), British Neuro-Oncology Society (BNOS) and Spanish Group for Cancer Immuno-Biotherapy (GÉTICA) are affiliated with Cancers and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Oncology) / CiteScore - Q1 (Oncology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 17.9 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Sections: published in 18 topical sections.
- Companion journals for Cancers include: Radiation and Onco.
Impact Factor:
5.2 (2022);
5-Year Impact Factor:
5.6 (2022)
Latest Articles
Synergistic Action of Benzyl Isothiocyanate and Sorafenib in a Nanoparticle Delivery System for Enhanced Triple-Negative Breast Cancer Treatment
Cancers 2024, 16(9), 1695; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091695 - 26 Apr 2024
Abstract
Triple-negative breast cancer (TNBC) presents a therapeutic challenge due to its complex pathology and limited treatment options. Addressing this challenge, our study focuses on the effectiveness of combination therapy, which has recently become a critical strategy in cancer treatment, improving therapeutic outcomes and
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Triple-negative breast cancer (TNBC) presents a therapeutic challenge due to its complex pathology and limited treatment options. Addressing this challenge, our study focuses on the effectiveness of combination therapy, which has recently become a critical strategy in cancer treatment, improving therapeutic outcomes and combating drug resistance and metastasis. We explored a novel combination therapy employing Benzyl isothiocyanate (BITC) and Sorafenib (SOR) and their nanoformulation, aiming to enhance therapeutic outcomes against TNBC. Through a series of in vitro assays, we assessed the cytotoxic effects of BITC and SOR, both free and encapsulated. The BITC–SOR-loaded nanoparticles (NPs) were synthesized using an amphiphilic copolymer, which demonstrated a uniform spherical morphology and favorable size distribution. The encapsulation efficiencies, as well as the sustained release profiles at varied pH levels, were quantified, revealing distinct kinetics that were well-modeled by the Korsmeyer–Peppas equation. The NP delivery system showed a marked dose-dependent cytotoxicity towards TNBC cells, with an IC50 of 7.8 μM for MDA-MB-231 cells, indicating improved efficacy over free drugs, while exhibiting minimal toxicity toward normal breast cells. Furthermore, the NPs significantly inhibited cell migration and invasion in TNBC models, surpassing the effects of free drugs. These findings underscore the potential of BITC–SOR-NPs as a promising therapeutic approach for TNBC, offering targeted delivery while minimizing systemic toxicity.
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(This article belongs to the Special Issue Triple Negative Breast Cancer Therapy Resistance and Metastasis)
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Open AccessReview
Proton Therapy in Non-Rhabdomyosarcoma Soft Tissue Sarcomas of Children and Adolescents
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Sabina Vennarini, Francesca Colombo, Alfredo Mirandola, Ester Orlandi, Emilia Pecori, Stefano Chiaravalli, Maura Massimino, Michela Casanova and Andrea Ferrari
Cancers 2024, 16(9), 1694; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091694 - 26 Apr 2024
Abstract
This paper provides insights into the use of Proton Beam Therapy (PBT) in pediatric patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). NRSTS are a heterogeneous group of rare and aggressive mesenchymal extraskeletal tumors, presenting complex and challenging clinical management scenarios. The overall survival
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This paper provides insights into the use of Proton Beam Therapy (PBT) in pediatric patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). NRSTS are a heterogeneous group of rare and aggressive mesenchymal extraskeletal tumors, presenting complex and challenging clinical management scenarios. The overall survival rate for patients with NRSTS is around 70%, but the outcome is strictly related to the presence of various variables, such as the histological subtype, grade of malignancy and tumor stage at diagnosis. Multimodal therapy is typically considered the preferred treatment for high-grade NRSTS. Radiotherapy plays a key role in the treatment of children and adolescents with NRSTS. However, the potential for radiation-induced side effects partially limits its use. Therefore, PBT represents a very suitable therapeutic option for these patients. The unique depth-dose characteristics of protons can be leveraged to minimize doses to healthy tissue significantly, potentially allowing for increased tumor doses and enhanced preservation of surrounding tissues. These benefits suggest that PBT may improve local control while reducing toxicity and improving quality of life. While clear evidence of therapeutic superiority of PBT over other modern photon techniques in NRSTS is still lacking—partly due to the limited data available—PBT can be an excellent treatment option for young patients with these tumors. A dedicated international comprehensive collaborative approach is essential to better define its role within the multidisciplinary management of NRSTS. Shared guidelines for PBT indications—based on the patient’s age, estimated outcome, and tumor location—and centralization in high-level referral centers are needed to optimize the use of resources, since access to PBT remains a challenge due to the limited number of available proton therapy facilities.
Full article
(This article belongs to the Section Pediatric Oncology)
Open AccessArticle
Genomic Characterization of Partial Tandem Duplication Involving the KMT2A Gene in Adult Acute Myeloid Leukemia
by
Andrew Seto, Gregory Downs, Olivia King, Shabnam Salehi-Rad, Ana Baptista, Kayu Chin, Sylvie Grenier, Bevoline Nwachukwu, Anne Tierens, Mark D. Minden, Adam C. Smith and José-Mario Capo-Chichi
Cancers 2024, 16(9), 1693; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091693 - 26 Apr 2024
Abstract
Background: Gene rearrangements affecting KMT2A are frequent in acute myeloid leukemia (AML) and are often associated with a poor prognosis. KMT2A gene fusions are often detected by chromosome banding analysis and confirmed by fluorescence in situ hybridization. However, small intragenic insertions, termed KMT2A
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Background: Gene rearrangements affecting KMT2A are frequent in acute myeloid leukemia (AML) and are often associated with a poor prognosis. KMT2A gene fusions are often detected by chromosome banding analysis and confirmed by fluorescence in situ hybridization. However, small intragenic insertions, termed KMT2A partial tandem duplication (KMT2A-PTD), are particularly challenging to detect using standard molecular and cytogenetic approaches. Methods: We have validated the use of a custom hybrid-capture-based next-generation sequencing (NGS) panel for comprehensive profiling of AML patients seen at our institution. This NGS panel targets the entire consensus coding DNA sequence of KMT2A. To deduce the presence of a KMT2A-PTD, we used the relative ratio of KMT2A exons coverage. We sought to corroborate the KMT2A-PTD NGS results using (1) multiplex-ligation probe amplification (MLPA) and (2) optical genome mapping (OGM). Results: We analyzed 932 AML cases and identified 41 individuals harboring a KMT2A-PTD. MLPA, NGS, and OGM confirmed the presence of a KMT2A-PTD in 22 of the cases analyzed where orthogonal testing was possible. The two false-positive KMT2A-PTD calls by NGS could be explained by the presence of cryptic structural variants impacting KMT2A and interfering with KMT2A-PTD analysis. OGM revealed the nature of these previously undetected gene rearrangements in KMT2A, while MLPA yielded inconclusive results. MLPA analysis for KMT2A-PTD is limited to exon 4, whereas NGS and OGM resolved KMT2A-PTD sizes and copy number levels. Conclusions: KMT2A-PTDs are complex gene rearrangements that cannot be fully ascertained using a single genomic platform. MLPA, NGS panels, and OGM are complementary technologies applied in standard-of-care testing for AML patients. MLPA and NGS panels are designed for targeted copy number analysis; however, our results showed that integration of concurrent genomic alterations is needed for accurate KMT2A-PTD identification. Unbalanced chromosomal rearrangements overlapping with KMT2A can interfere with the diagnostic sensitivity and specificity of copy-number-based KMT2A-PTD detection methodologies.
Full article
(This article belongs to the Special Issue Optical Genome Mapping in Hematological Malignancies)
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Open AccessSystematic Review
The Association between Blood Test Trends and Undiagnosed Cancer: A Systematic Review and Critical Appraisal
by
Pradeep S. Virdee, Kiana K. Collins, Claire Friedemann Smith, Xin Yang, Sufen Zhu, Sophie E. Roberts, Nia Roberts, Jason L. Oke, Clare Bankhead, Rafael Perera, FD Richard Hobbs and Brian D. Nicholson
Cancers 2024, 16(9), 1692; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091692 - 26 Apr 2024
Abstract
Clinical guidelines include monitoring blood test abnormalities to identify patients at increased risk of undiagnosed cancer. Noting blood test changes over time may improve cancer risk stratification by considering a patient’s individual baseline and important changes within the normal range. We aimed to
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Clinical guidelines include monitoring blood test abnormalities to identify patients at increased risk of undiagnosed cancer. Noting blood test changes over time may improve cancer risk stratification by considering a patient’s individual baseline and important changes within the normal range. We aimed to review the published literature to understand the association between blood test trends and undiagnosed cancer. MEDLINE and EMBASE were searched until 15 May 2023 for studies assessing the association between blood test trends and undiagnosed cancer. We used descriptive summaries and narratively synthesised studies. We included 29 articles. Common blood tests were haemoglobin (24%, n = 7), C-reactive protein (17%, n = 5), and fasting blood glucose (17%, n = 5), and common cancers were pancreatic (29%, n = 8) and colorectal (17%, n = 5). Of the 30 blood tests studied, an increasing trend in eight (27%) was associated with eight cancer types, and a decreasing trend in 17 (57%) with 10 cancer types. No association was reported between trends in 11 (37%) tests and breast, bile duct, glioma, haematological combined, liver, prostate, or thyroid cancers. Our review highlights trends in blood tests that could facilitate the identification of individuals at increased risk of undiagnosed cancer. For most possible combinations of tests and cancers, there was limited or no evidence.
Full article
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
Open AccessReview
Update in the Treatment of Pleural Tumors: Robotic Surgery Combined with Hyperthermic Intrathoracic Chemotherapy
by
Gaetano Romano, Carmelina Cristina Zirafa, Ilaria Ceccarelli, Gianmarco Elia, Federico Davini and Franca Melfi
Cancers 2024, 16(9), 1691; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091691 - 26 Apr 2024
Abstract
(1) Background. Intracavitary hyperthermic chemotherapy (HITHOC) remains part of the complex mosaic that is the multimodal approach for advanced stage thymoma and pleural malignancies. However, robotic pleurectomy/removal of pleural lesions in combination with intrathoracic chemotherapy is not currently being investigated. The aim of
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(1) Background. Intracavitary hyperthermic chemotherapy (HITHOC) remains part of the complex mosaic that is the multimodal approach for advanced stage thymoma and pleural malignancies. However, robotic pleurectomy/removal of pleural lesions in combination with intrathoracic chemotherapy is not currently being investigated. The aim of this study is to evaluate the safety of robotic pleurectomy/removal of relapses and HITHOC in patients with pleural recurrence of thymoma or MPM. (2) Methods: The data of nine consecutive patients affected by thymoma relapses or MPM who underwent robotic surgery in combination with HITHOC from February 2017 to November 2022 were collected and analyzed. Surgery performed prior to intrathoracic infusion of high-temperature chemotherapy consisted of removal of recurrences (three patients) or pleurectomy (six patients). All surgeries were performed with a four-port, fully robotic technique. (3) Results: No intraoperative complications occurred. No renal complications related to infusion were recorded. One patient, who underwent pleurectomy for MPM, had a grade II Clavien–Dindo postoperative complication. Oncological follow-up showed results in line with the literature. (4) Conclusion: With the limitation of the small number of patients, robotic surgery in combination with HITHOC seems to be safe in patients with pleural relapses of thymoma and early-stage MPM.
Full article
(This article belongs to the Section Cancer Biomarkers)
Open AccessReview
Current and Future Therapeutic Targets for Directed Molecular Therapies in Cholangiocarcinoma
by
Philipp Heumann, Andreas Albert, Karsten Gülow, Denis Tümen, Martina Müller and Arne Kandulski
Cancers 2024, 16(9), 1690; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091690 - 26 Apr 2024
Abstract
We conducted a comprehensive review of the current literature of published data, clinical trials (MEDLINE; ncbi.pubmed.com), congress contributions (asco.org; esmo.org), and active recruiting clinical trains (clinicaltrial.gov) on targeted therapies in cholangiocarcinoma. Palliative treatment regimens were analyzed as well as preoperative and perioperative treatment
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We conducted a comprehensive review of the current literature of published data, clinical trials (MEDLINE; ncbi.pubmed.com), congress contributions (asco.org; esmo.org), and active recruiting clinical trains (clinicaltrial.gov) on targeted therapies in cholangiocarcinoma. Palliative treatment regimens were analyzed as well as preoperative and perioperative treatment options. We summarized the current knowledge for each mutation and molecular pathway that is or has been under clinical evaluation and discussed the results on the background of current treatment guidelines. We established and recommended targeted treatment options that already exist for second-line settings, including IDH-, BRAF-, and NTRK-mutated tumors, as well as for FGFR2 fusion, HER2/neu-overexpression, and microsatellite instable tumors. Other options for targeted treatment include EGFR- or VEGF-dependent pathways, which are known to be overexpressed or dysregulated in this cancer type and are currently under clinical investigation. Targeted therapy in CCA is a hallmark of individualized medicine as these therapies aim to specifically block pathways that promote cancer cell growth and survival, leading to tumor shrinkage and improved patient outcomes based on the molecular profile of the tumor.
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(This article belongs to the Special Issue New Insights into the Management of Intrahepatic Cholangiocarcinoma)
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Open AccessArticle
A Simple Frailty Score Predicts Survival and Early Mortality in Systemic AL Amyloidosis
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Rafael Ríos-Tamayo, Ramón Lecumberri, María Teresa Cibeira, Verónica González-Calle, Rafael Alonso, Amalia Domingo-González, Elena Landete, Cristina Encinas, Belén Iñigo, María-Jesús Blanchard, Elena Alejo, Isabel Krsnik, Manuel Gómez-Bueno, Pablo Garcia-Pavia, Javier Segovia-Cubero, Laura Rosiñol, Juan-José Lahuerta, Joaquín Martínez-López and Joan Bladé
Cancers 2024, 16(9), 1689; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091689 - 26 Apr 2024
Abstract
Systemic AL amyloidosis is a challenging disease for which many patients are considered frail in daily clinical practice. However, no study has so far addressed frailty and its impact on the outcome of these patients. We built a simple score to predict mortality
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Systemic AL amyloidosis is a challenging disease for which many patients are considered frail in daily clinical practice. However, no study has so far addressed frailty and its impact on the outcome of these patients. We built a simple score to predict mortality based on three frailty-associated variables: age, ECOG performance status (<2 vs. ≥2) and NT-proBNP (<8500 vs. ≥8500 ng/L). Four-hundred and sixteen consecutive newly diagnosed patients diagnosed at ten sites from the Spanish Myeloma Group were eligible for the study. The score was developed in a derivation cohort from a referral center, and it was externally validated in a multicenter cohort. Multivariate analysis showed that the three variables were independent predictors of survival. The score was able to discriminate four groups of patients in terms of overall survival and early mortality in both cohorts. Comorbidity was also analyzed with the Charlson comorbidity index, but it did not reach statistical significance in the model. A nomogram was created to easily estimate the mortality risk of each patient at each time point. This score is a simple, robust, and efficient approach to dynamically assess frailty-dependent mortality both at diagnosis and throughout follow-up. The optimal treatment for frail AL amyloidosis patients remains to be determined but we suggest that the estimation of frailty-associated risk could complement current staging systems, adding value in clinical decision-making in this complex scenario.
Full article
(This article belongs to the Section Clinical Research of Cancer)
Open AccessArticle
Association of miR-146a-5p and miR-21-5p with Prognostic Features in Melanomas
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Maria Naddeo, Elisabetta Broseghini, Federico Venturi, Sabina Vaccari, Barbara Corti, Martina Lambertini, Costantino Ricci, Beatrice Fontana, Giorgio Durante, Milena Pariali, Biagio Scotti, Giulia Milani, Elena Campione, Manuela Ferracin and Emy Dika
Cancers 2024, 16(9), 1688; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091688 - 26 Apr 2024
Abstract
Background: Cutaneous melanoma (CM) is one of the most lethal tumors among skin cancers and its incidence is rising worldwide. Recent data support the role of microRNAs (miRNAs) in melanoma carcinogenesis and their potential use as disease biomarkers. Methods: We quantified the expression
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Background: Cutaneous melanoma (CM) is one of the most lethal tumors among skin cancers and its incidence is rising worldwide. Recent data support the role of microRNAs (miRNAs) in melanoma carcinogenesis and their potential use as disease biomarkers. Methods: We quantified the expression of miR-146a-5p and miR-21-5p in 170 formalin-fixed paraffin embedded (FFPE) samples of CM, namely 116 superficial spreading melanoma (SSM), 26 nodular melanoma (NM), and 28 lentigo maligna melanoma (LMM). We correlated miRNA expression with specific histopathologic features including Breslow thickness (BT), histological subtype, ulceration and regression status, and mitotic index. Results: miR-146a-5p and miR-21-5p were significantly higher in NM compared to SSM and LMM. The positive correlation between miR-146a-5p and miR-21-5p expression and BT was confirmed for both miRNAs in SSM. Considering the ulceration status, we assessed that individual miR-21-5p expression was significantly higher in ulcerated CMs. The increased combined expression of the two miRNAs was strongly associated with ulceration (p = 0.0093) and higher mitotic rate (≥1/mm2) (p = 0.0005). We demonstrated that the combination of two-miRNA expression and prognostic features (BT and ulceration) can better differentiate cutaneous melanoma prognostic groups, considering overall survival and time-to-relapse clinical outcomes. Specifically, miRNA expression can further stratify prognostic groups among patients with BT ≥ 0.8 mm but without ulceration. Our findings provide further insights into the characterization of CM with specific prognostic features. The graphical abstract was created with BioRender.com.
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(This article belongs to the Special Issue Melanoma: Clinical Trials and Translational Research)
Open AccessArticle
Development of an Artificial-Intelligence-Based Tool for Automated Assessment of Cellularity in Bone Marrow Biopsies in Ph-Negative Myeloproliferative Neoplasms
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Giuseppe D’Abbronzo, Antonio D’Antonio, Annarosaria De Chiara, Luigi Panico, Lucianna Sparano, Anna Diluvio, Antonello Sica, Gino Svanera, Renato Franco and Andrea Ronchi
Cancers 2024, 16(9), 1687; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091687 - 26 Apr 2024
Abstract
The cellularity assessment in bone marrow biopsies (BMBs) for the diagnosis of Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is a key diagnostic feature and is usually performed by the human eyes through an optical microscope with consequent inter-observer and intra-observer variability. Thus, the
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The cellularity assessment in bone marrow biopsies (BMBs) for the diagnosis of Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is a key diagnostic feature and is usually performed by the human eyes through an optical microscope with consequent inter-observer and intra-observer variability. Thus, the use of an automated tool may reduce variability, improving the uniformity of the evaluation. The aim of this work is to develop an accurate AI-based tool for the automated quantification of cellularity in BMB histology. A total of 55 BMB histological slides, diagnosed as Ph- MPN between January 2018 and June 2023 from the archives of the Pathology Unit of University “Luigi Vanvitelli” in Naples (Italy), were scanned on Ventana DP200 or Epredia P1000 and exported as whole-slide images (WSIs). Fifteen BMBs were randomly selected to obtain a training set of AI-based tools. An expert pathologist and a trained resident performed annotations of hematopoietic tissue and adipose tissue, and annotations were exported as .tiff images and .png labels with two colors (black for hematopoietic tissue and yellow for adipose tissue). Subsequently, we developed a semantic segmentation model for hematopoietic tissue and adipose tissue. The remaining 40 BMBs were used for model verification. The performance of our model was compared with an evaluation of the cellularity of five expert hematopathologists and three trainees; we obtained an optimal concordance between our model and the expert pathologists’ evaluation, with poorer concordance for trainees. There were no significant differences in cellularity assessments between two different scanners.
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(This article belongs to the Special Issue Quantitative Imaging and Digital Pathology in Clinical Cancer Research)
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Open AccessReview
Digital Pathology for Better Clinical Practice
by
Assia Hijazi, Carlo Bifulco, Pamela Baldin and Jérôme Galon
Cancers 2024, 16(9), 1686; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091686 - 26 Apr 2024
Abstract
(1) Background: Digital pathology (DP) is transforming the landscape of clinical practice, offering a revolutionary approach to traditional pathology analysis and diagnosis. (2) Methods: This innovative technology involves the digitization of traditional glass slides which enables pathologists to access, analyze, and share high-resolution
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(1) Background: Digital pathology (DP) is transforming the landscape of clinical practice, offering a revolutionary approach to traditional pathology analysis and diagnosis. (2) Methods: This innovative technology involves the digitization of traditional glass slides which enables pathologists to access, analyze, and share high-resolution whole-slide images (WSI) of tissue specimens in a digital format. By integrating cutting-edge imaging technology with advanced software, DP promises to enhance clinical practice in numerous ways. DP not only improves quality assurance and standardization but also allows remote collaboration among experts for a more accurate diagnosis. Artificial intelligence (AI) in pathology significantly improves cancer diagnosis, classification, and prognosis by automating various tasks. It also enhances the spatial analysis of tumor microenvironment (TME) and enables the discovery of new biomarkers, advancing their translation for therapeutic applications. (3) Results: The AI-driven immune assays, Immunoscore (IS) and Immunoscore-Immune Checkpoint (IS-IC), have emerged as powerful tools for improving cancer diagnosis, prognosis, and treatment selection by assessing the tumor immune contexture in cancer patients. Digital IS quantitative assessment performed on hematoxylin–eosin (H&E) and CD3+/CD8+ stained slides from colon cancer patients has proven to be more reproducible, concordant, and reliable than expert pathologists’ evaluation of immune response. Outperforming traditional staging systems, IS demonstrated robust potential to enhance treatment efficiency in clinical practice, ultimately advancing cancer patient care. Certainly, addressing the challenges DP has encountered is essential to ensure its successful integration into clinical guidelines and its implementation into clinical use. (4) Conclusion: The ongoing progress in DP holds the potential to revolutionize pathology practices, emphasizing the need to incorporate powerful AI technologies, including IS, into clinical settings to enhance personalized cancer therapy.
Full article
(This article belongs to the Special Issue Predictive Biomarkers for Colorectal Cancer)
Open AccessArticle
Feasibility and Acute Toxicity of Hypo-Fractionated Radiotherapy on 0.35T MR-LINAC: The First Prospective Study in Spain
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Daniela Gonsalves, Abrahams Ocanto, Eduardo Meilan, Alberto Gomez, Jesus Dominguez, Lisselott Torres, Castalia Fernández Pascual, Macarena Teja, Miguel Montijano Linde, Marcos Guijarro, Daniel Rivas, Jose Begara, Jose Antonio González, Jon Andreescu, Esther Holgado, Diego Alcaraz, Escarlata López, Maia Dzhugashvli, Fernando Lopez-Campos, Filippo Alongi and Felipe Couñagoadd
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Cancers 2024, 16(9), 1685; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091685 - 26 Apr 2024
Abstract
This observational, descriptive, longitudinal, and prospective basket-type study (Registry #5289) prospectively evaluated the feasibility and acute toxicity of hypo-fractionated radiotherapy on the first 0.35T MR-LINAC in Spain. A total of 37 patients were included between August and December 2023, primarily with prostate tumors
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This observational, descriptive, longitudinal, and prospective basket-type study (Registry #5289) prospectively evaluated the feasibility and acute toxicity of hypo-fractionated radiotherapy on the first 0.35T MR-LINAC in Spain. A total of 37 patients were included between August and December 2023, primarily with prostate tumors (59.46%), followed by pancreatic tumors (32.44%). Treatment regimens typically involved extreme hypo-fractionated radiotherapy, with precise dose delivery verified through quality assurance measures. Acute toxicity assessment at treatment completion revealed manageable cystitis, with one case persisting at the three-month follow-up. Gastrointestinal toxicity was minimal. For pancreatic tumors, daily adaptation of organ-at-risk (OAR) and gross tumor volume (GTV) was practiced, with median doses to OAR within acceptable limits. Three patients experienced gastrointestinal toxicity, mainly nausea. Overall, the study demonstrates the feasibility and safety of extreme hypo-fractionated radiotherapy on a 0.35T MR-LINAC, especially for challenging anatomical sites like prostate and pancreatic tumors. These findings support the feasibility of MR-LINAC-based radiotherapy in delivering precise treatments with minimal toxicity, highlighting its potential for optimizing cancer treatment strategies.
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(This article belongs to the Special Issue MRI-Guided Real-Time Adaptive Radiotherapy)
Open AccessArticle
Assessing the Predictive Accuracy of EORTC, CUETO and EAU Risk Stratification Models for High-Grade Recurrence and Progression after Bacillus Calmette–Guérin Therapy in Non-Muscle-Invasive Bladder Cancer
by
Aleksander Ślusarczyk, Karolina Garbas, Patryk Pustuła, Łukasz Zapała and Piotr Radziszewski
Cancers 2024, 16(9), 1684; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091684 - 26 Apr 2024
Abstract
The currently available EORTC, CUETO and EAU2021 risk stratifications were originally developed to predict recurrence and progression in non-muscle-invasive bladder cancer (NMIBC). However, they have not been validated to differentiate between high-grade (HG) and low-grade (LG) recurrence-free survival (RFS), which are distinct events
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The currently available EORTC, CUETO and EAU2021 risk stratifications were originally developed to predict recurrence and progression in non-muscle-invasive bladder cancer (NMIBC). However, they have not been validated to differentiate between high-grade (HG) and low-grade (LG) recurrence-free survival (RFS), which are distinct events with specific implications. We aimed to evaluate the accuracy of available risk models and identify additional risk factors for HG RFS and PFS among NMIBC patients treated with Bacillus Calmette–Guérin (BCG). We retrospectively included 171 patients who underwent transurethral resection of the bladder tumor (TURBT), of whom 73 patients (42.7%) experienced recurrence and 29 (17%) developed progression. Initially, there were 21 low-grade and 52 high-grade recurrences. EORTC2006, EORTC2016 and CUETO recurrence scoring systems lacked accuracy in the prediction of HG RFS (C-index 0.63/0.55/0.59, respectively). EAU2021 risk stratification, EORTC2006, EORTC2016, and CUETO progression scoring systems demonstrated low to moderate accuracy (C-index 0.59/0.68/0.65/0.65) in the prediction of PFS. In the multivariable analysis, T1HG at repeat TURBT (HR = 3.17 p < 0.01), tumor multiplicity (HR = 2.07 p < 0.05), previous history of HG NMIBC (HR = 2.37 p = 0.06) and EORTC2006 progression risk score (HR = 1.1 p < 0.01) were independent predictors for HG RFS. To conclude, available risk models lack accuracy in predicting HG RFS and PFS in -NMIBC patients treated with BCG.
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(This article belongs to the Special Issue Prognostic Factors in Urologic Cancers—Assessment and Integration into Clinical Care)
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Open AccessReview
Retreatment with Immune Checkpoint Inhibitors in the New Scenario of Immunotherapy in Non-Small Cell Lung Cancer
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Sabrina Rossi, Silvia Masini, Giovanna Finocchiaro, Elena Lorenzi, Luca Toschi and Armando Santoro
Cancers 2024, 16(9), 1683; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091683 - 26 Apr 2024
Abstract
The advent of immunotherapy has transformed the treatment paradigm for metastatic non-small cell lung cancer (NSCLC). In the past few years, several studies have investigated the potential role of immune checkpoint inhibitors (ICIs) in resectable and unresectable locally advanced disease, achieving remarkable results
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The advent of immunotherapy has transformed the treatment paradigm for metastatic non-small cell lung cancer (NSCLC). In the past few years, several studies have investigated the potential role of immune checkpoint inhibitors (ICIs) in resectable and unresectable locally advanced disease, achieving remarkable results that led to their approval in clinical practice. However, there is limited evidence on immunotherapy rechallenge after recurrence, with the majority of available knowledge coming from retrospective studies which involve heavily pretreated patients with advanced NSCLC. The recent introduction in the curative setting and the potential regulatory restrictions raise questions about the optimal choice of first-line and subsequent therapies for patients with systemic relapse. The role of immunotherapy readministration in this new scenario needs to be clarified, as well as the identification of patients for whom it is more appropriate, including clinical characteristics, duration of response, switching to other ICIs, reasons for discontinuation and immune-related toxicity. Here, we review literature on rechallenge with immunotherapy, including efficacy, safety profile and potential predictive factors of response.
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(This article belongs to the Special Issue 2nd Edition: Imaging and Therapy in Lung Cancer and Mesothelioma)
Open AccessArticle
BRCA1/2 Testing Landscape in Ovarian Cancer: A Nationwide, Real-World Data Study
by
Lieke Lanjouw, Joost Bart, Marian J. E. Mourits, Stefan M. Willems, Annemieke H. van der Hout, Arja ter Elst and Geertruida H. de Bock
Cancers 2024, 16(9), 1682; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091682 - 26 Apr 2024
Abstract
Analyzing BRCA1/2 tumor pathogenic variants (TPVs) in epithelial tubal/ovarian cancers (EOCs) has become an essential part of the diagnostic workflow in many centers to guide treatment options and genetic cascade testing. However, there is no standardization of testing procedures, including techniques, gene assays,
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Analyzing BRCA1/2 tumor pathogenic variants (TPVs) in epithelial tubal/ovarian cancers (EOCs) has become an essential part of the diagnostic workflow in many centers to guide treatment options and genetic cascade testing. However, there is no standardization of testing procedures, including techniques, gene assays, or sequencers used, and data on the execution of tumor tests remains scarce. Therefore, we evaluated characteristics of BRCA1/2 tumor testing in advanced-stage EOC with real-world national data. Pathology reports of patients diagnosed with EOC in 2019 in the Netherlands were obtained from the Dutch Pathology Registry (PALGA), and data regarding histological subtype and BRCA1/2 tumor tests were extracted. A total of 999 patients with advanced-stage EOC were included. Tumor tests were performed for 502 patients (50.2%) and BRCA1/2 TPVs were detected in 14.7%. Of all tests, 48.6% used hybrid capture techniques and 26.5% used PCR-based techniques. More than half of the tests (55.0%) analyzed other genes in addition to BRCA1/2. Overall, this study highlights the heterogeneity in the execution of BRCA1/2 tumor tests. Despite a lack of evidence of quality differences, we emphasize that adequate reporting and internal and external quality monitors are essential for the high-quality implementation and execution of reliable BRCA1/2 tumor testing, which is crucial for identifying all patients with BRCA1/2 TPVs.
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(This article belongs to the Section Cancer Pathophysiology)
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Extracellular Vesicles for Childhood Cancer Liquid Biopsy
by
Nilubon Singhto, Pongpak Pongphitcha, Natini Jinawath, Suradej Hongeng and Somchai Chutipongtanate
Cancers 2024, 16(9), 1681; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091681 - 26 Apr 2024
Abstract
Liquid biopsy involves the utilization of minimally invasive or noninvasive techniques to detect biomarkers in biofluids for disease diagnosis, monitoring, or guiding treatments. This approach is promising for the early diagnosis of childhood cancer, especially for brain tumors, where tissue biopsies are more
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Liquid biopsy involves the utilization of minimally invasive or noninvasive techniques to detect biomarkers in biofluids for disease diagnosis, monitoring, or guiding treatments. This approach is promising for the early diagnosis of childhood cancer, especially for brain tumors, where tissue biopsies are more challenging and cause late detection. Extracellular vesicles offer several characteristics that make them ideal resources for childhood cancer liquid biopsy. Extracellular vesicles are nanosized particles, primarily secreted by all cell types into body fluids such as blood and urine, and contain molecular cargos, i.e., lipids, proteins, and nucleic acids of original cells. Notably, the lipid bilayer-enclosed structure of extracellular vesicles protects their cargos from enzymatic degradation in the extracellular milieu. Proteins and nucleic acids of extracellular vesicles represent genetic alterations and molecular profiles of childhood cancer, thus serving as promising resources for precision medicine in cancer diagnosis, treatment monitoring, and prognosis prediction. This review evaluates the recent progress of extracellular vesicles as a liquid biopsy platform for various types of childhood cancer, discusses the mechanistic roles of molecular cargos in carcinogenesis and metastasis, and provides perspectives on extracellular vesicle-guided therapeutic intervention. Extracellular vesicle-based liquid biopsy for childhood cancer may ultimately contribute to improving patient outcomes.
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(This article belongs to the Special Issue Advances in Multi-Omics of Pediatric, Adolescence and Young Adult Cancers)
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A Re-Examination of Neoadjuvant Therapy for Thymic Tumors: A Long and Winding Road
by
Fenghao Yu, Zhitao Gu, Xuefei Zhang, Ning Xu, Xiuxiu Hao, Changlu Wang, Yizhuo Zhao, Teng Mao and Wentao Fang
Cancers 2024, 16(9), 1680; https://doi.org/10.3390/cancers16091680 - 26 Apr 2024
Abstract
For most patients with advanced thymic epithelial tumors (TETs), a complete resection is a strong indicator of a better prognosis. But sometimes, primary surgery is unsatisfactory, and preoperative therapy is needed to facilitate complete resection. Neoadjuvant chemotherapy is the most used form of
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For most patients with advanced thymic epithelial tumors (TETs), a complete resection is a strong indicator of a better prognosis. But sometimes, primary surgery is unsatisfactory, and preoperative therapy is needed to facilitate complete resection. Neoadjuvant chemotherapy is the most used form of preoperative therapy. But studies on neoadjuvant chemotherapy have included mainly patients with thymoma; its efficacy in patients with thymic carcinoma is less known. Neoadjuvant chemoradiation has also been explored in a few studies. Novel therapies such as immunotherapy and targeted therapy have shown efficacy in patients with recurrent/metastatic TETs as a second-line option; their role as preoperative therapy is still under investigation. In this review, we discuss the existing evidence on preoperative therapy and the insight it provides for current clinical practice and future studies.
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(This article belongs to the Special Issue Thymic Tumors: New Developments and Future Directions in Molecularly Informed Therapies)
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Advances in Molecular Understanding of Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis: Towards Precision Medicine
by
Hammad Tashkandi and Ismail Elbaz Younes
Cancers 2024, 16(9), 1679; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091679 - 26 Apr 2024
Abstract
Myeloproliferative neoplasms (MPNs), including Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF), are characterized by the clonal proliferation of hematopoietic stem cells leading to an overproduction of hematopoietic cells. The last two decades have seen significant advances in our understanding of
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Myeloproliferative neoplasms (MPNs), including Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF), are characterized by the clonal proliferation of hematopoietic stem cells leading to an overproduction of hematopoietic cells. The last two decades have seen significant advances in our understanding of the molecular pathogenesis of these diseases, with the discovery of key mutations in the JAK2, CALR, and MPL genes being pivotal. This review provides a comprehensive update on the molecular landscape of PV, ET, and PMF, highlighting the diagnostic, prognostic, and therapeutic implications of these genetic findings. We delve into the challenges of diagnosing and treating patients with prognostic mutations, clonal evolution, and the impact of emerging technologies like next-generation sequencing and single-cell genomics on the field. The future of MPN management lies in leveraging these molecular insights to develop personalized treatment strategies, aiming for precision medicine that optimizes outcomes for patients. This article synthesizes current knowledge on molecular diagnostics in MPNs, underscoring the critical role of genetic profiling in enhancing patient care and pointing towards future research directions that promise to further refine our approach to these complex disorders.
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(This article belongs to the Special Issue Molecular and Genetic Diagnosis and Targeted Therapy of Myeloproliferative Neoplasms)
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Proteins Involved in Focal Cell Adhesion and Podosome Formation Are Differentially Expressed during Colorectal Tumorigenesis in AOM-Treated Rats
by
Ian X. Swain and Adam M. Kresak
Cancers 2024, 16(9), 1678; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091678 - 26 Apr 2024
Abstract
Colorectal tumorigenesis involves the development of aberrant crypt foci (ACF) or preneoplastic lesions, representing the earliest morphological lesion visible in colon cancer. The purpose of this study was to determine changes in protein expression in carcinogen-induced ACF as they mature and transform into
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Colorectal tumorigenesis involves the development of aberrant crypt foci (ACF) or preneoplastic lesions, representing the earliest morphological lesion visible in colon cancer. The purpose of this study was to determine changes in protein expression in carcinogen-induced ACF as they mature and transform into adenomas. Protein expression profiles of azoxymethane (AOM)-induced F344 rat colon ACF and adenomas were compared at four time points, 4 (control), 8, 16, and 24 weeks post AOM administration (n = 9/group), with time points correlating with induction and transformation events. At each time point, micro-dissected ACF and/or adenoma tissues were analyzed across multiple quantitative two-dimensional (2D-DIGE) gels using a Cy-dye labeling technique and a pooled internal standard to quantify expression changes with statistical confidence. Western blot and subsequent network pathway mapping were used to confirm and elucidate differentially expressed (p ≤ 0.05) proteins, including changes in vinculin (Vcl; p = 0.007), scinderin (Scin; p = 0.02), and profilin (Pfn1; p = 0.01), By determining protein expression changes in ACF as they mature and transform into adenomas, a “baseline” of altered regulatory proteins associated with adenocarcinoma development in this model has been elucidated. These data will enable future studies aimed at biomarker identification and understanding the molecular biology of intestinal tumorigenesis and adenocarcinoma maturation under varying intestinal conditions.
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(This article belongs to the Section Molecular Cancer Biology)
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Internet Access and Use by Patients with Gynecologic Malignancies: A Cross-Sectional Study
by
Frederik Bach, David Engelhardt, Christoph A. Mallmann, Sina Tamir, Lars Schröder, Christian M. Domröse and Michael R. Mallmann
Cancers 2024, 16(9), 1677; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091677 - 26 Apr 2024
Abstract
The influence of digitalization on information-seeking, decision-making properties of patients, therapy monitoring, and patient–physician interactions has and will change the global health sector tremendously. With this study, we add knowledge on the degree of digitalization, digital device availability, the use and availability of
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The influence of digitalization on information-seeking, decision-making properties of patients, therapy monitoring, and patient–physician interactions has and will change the global health sector tremendously. With this study, we add knowledge on the degree of digitalization, digital device availability, the use and availability of home and mobile internet access, and the willingness to use novel forms of patient–physician interactions in a group of gynecologic cancer patients. From July 2017 to March 2022, 150 women with a diagnosis of gynecologic malignancy at the University Hospital of Cologne participated in this questionnaire-based cohort study. Any one of three potential internet access devices (stationary computer, smartphone, or tablet) is owned by 94% of patients and the only patient intrinsic factor that is significantly associated with the property of any one of these internet access devices is age. The Internet is used daily or several times per week to assess information on their disease by 92.8%, 90.1% use the Internet for communicational purposes and 71.9% and 93.6% are willing to communicate with their treating physicians via E-Mail or even novel forms of communication, respectively. In conclusion, the predominant majority of gynecologic cancer patients can be reached by modern internet-based E-Health technologies.
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(This article belongs to the Special Issue Digital Health Technologies in Oncology)
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Feasibility and Short-Term Outcomes in Liver-First Approach: A Spanish Snapshot Study (the RENACI Project)
by
Mario Serradilla-Martín, Celia Villodre, Laia Falgueras-Verdaguer, Natalia Zambudio-Carroll, José T. Castell-Gómez, Juan L. Blas-Laina, Vicente Borrego-Estella, Carlos Domingo-del-Pozo, Gabriel García-Plaza, Francisco J. González-Rodríguez, Eva M. Montalvá-Orón, Ángel Moya-Herraiz, Sandra Paterna-López, Miguel A. Suárez-Muñoz, Maialen Alkorta-Zuloaga, Gerardo Blanco-Fernández, Enrique Dabán-Collado, Miguel A. Gómez-Bravo, José I. Miota-de-Llamas, Fernando Rotellar, Belinda Sánchez-Pérez, Santiago Sánchez-Cabús, David Pacheco-Sánchez, Juan C. Rodríguez-Sanjuan, María A. Varona-Bosque, Lucía Carrión-Álvarez, Sofía de la Serna-Esteban, Cristina Dopazo, Elena Martín-Pérez, David Martínez-Cecilia, María J. Castro-Santiago, Dimitri Dorcaratto, Marta L. Gutiérrez-Díaz, José M. Asencio-Pascual, Fernando Burdío-Pinilla, Roberto Carracedo-Iglesias, Alfredo Escartín-Arias, Benedetto Ielpo, Gonzalo Rodríguez-Laiz, Andrés Valdivieso-López, Emilio De-Vicente-López, Vicente Alonso-Orduña and José M. Ramiaadd
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Cancers 2024, 16(9), 1676; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16091676 - 26 Apr 2024
Abstract
(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes
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(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes in the liver-first approach. (2) Methods: A prospective observational study was performed in Spanish hospitals that had a medium/high-volume of HPB surgeries from 1 June 2019 to 31 August 2020. (3) Results: In total, 40 hospitals participated, including a total of 2288 hepatectomies, 1350 for colorectal liver metastases, 150 of them (11.1%) using the liver-first approach, 63 (42.0%) in hospitals performing <50 hepatectomies/year. The proportion of patients as ASA III was significantly higher in centers performing ≥50 hepatectomies/year (difference: 18.9%; p = 0.0213). In 81.1% of the cases, the primary tumor was in the rectum or sigmoid colon. In total, 40% of the patients underwent major hepatectomies. The surgical approach was open surgery in 87 (58.0%) patients. Resection margins were R0 in 78.5% of the patients. In total, 40 (26.7%) patients had complications after the liver resection and 36 (27.3%) had complications after the primary resection. One-hundred and thirty-two (89.3%) patients completed the therapeutic regime. (4) Conclusions: There were no differences in the surgical outcomes between the centers performing <50 and ≥50 hepatectomies/year. Further analysis evaluating factors associated with clinical outcomes and determining the best candidates for this approach will be subsequently conducted.
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(This article belongs to the Special Issue Treatment of Hepatopancreatobiliary Cancers: Open Question, Challenge, and Future Directions)
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