Cancers

15 pages, 843 KiB

Open AccessArticle

Extrahepatic Recurrence After Surgical Resection of Hepatocellular Carcinoma Without Intrahepatic Recurrence: A Multi-Institutional Observational Study

by Ga Ram You, Shin Young Park, Su Hyeon Cho, Sung Bum Cho, Yang Seok Ko, Chang Hun Lee, Hoon Gil Jo, Sung Kyu Choi and Jae Hyun Yoon

Cancers 2025, 17(9), 1417; https://doi.org/10.3390/cancers17091417 - 23 Apr 2025

Abstract

Background/Objectives: Extrahepatic recurrence (EHR) is a significant negative prognostic factor in hepatocellular carcinoma (HCC). Although EHR is commonly observed in high-risk patients following HCC hepatectomy, its occurrence without concurrent intrahepatic HCC remains poorly understood. Therefore, this study aims to examine the clinical characteristics [...] Read more.

Background/Objectives: Extrahepatic recurrence (EHR) is a significant negative prognostic factor in hepatocellular carcinoma (HCC). Although EHR is commonly observed in high-risk patients following HCC hepatectomy, its occurrence without concurrent intrahepatic HCC remains poorly understood. Therefore, this study aims to examine the clinical characteristics and risk factors associated with EHR in patients without intrahepatic HCC at diagnosis. Methods: This study included 1066 treatment-naïve patients who underwent curative hepatectomy for HCC at four tertiary academic centers between January 2004 and December 2019. After excluding those with intrahepatic recurrence (IHR), concurrent EHR, or incomplete clinical records, 569 patients were included in the final analysis. Risk factors for EHR were assessed using multivariate Cox regression over a median follow-up period of 3.91 years. Results: Among the cohort, 38 patients developed EHR post-surgery without residual intrahepatic HCC, with a median follow-up of 1.04 years. These patients experienced earlier initial HCC recurrence than those without EHR (1.73 vs. 4.43 years). Multivariate analysis revealed significant associations between EHR and microvascular invasion (hazard ratio [HR]: 2.418, p = 0.020), tumor necrosis (HR: 2.592, p = 0.009), and initial tumor staging beyond the Milan criteria (HR: 3.008, p = 0.001). Moreover, Cox regression analysis revealed that EHR strongly correlated with decreased post-hepatectomy survival (HR: 14.044, p < 0.001). Cumulative EHR and survival rates were closely linked to the number of risk factors present. Conclusions: EHR without detectable IHR is significant and warrants close monitoring in high-risk patients. Full article

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

12 pages, 248 KiB

Open AccessArticle

External Lymphatic Fistula After Radical Surgery for Colorectal Cancer: A Case Series

by Vincenzo Tondolo, Luca Emanuele Amodio, Federica Marzi, Giada Livadoti, Giuseppe Quero and Gianluca Rizzo

Cancers 2025, 17(9), 1416; https://doi.org/10.3390/cancers17091416 - 23 Apr 2025

Abstract

Background: The incidence of external lymphatic fistula (ELF) represents a relatively rare complication after surgery for colorectal cancer, especially in Western countries. However, the rate of this complication is progressively increasing following the introduction of complete mesocolic excision and central vascular ligation with [...] Read more.

Background: The incidence of external lymphatic fistula (ELF) represents a relatively rare complication after surgery for colorectal cancer, especially in Western countries. However, the rate of this complication is progressively increasing following the introduction of complete mesocolic excision and central vascular ligation with consequent extensive lymphadenectomy. There are no guidelines for the management of ELF, with therapeutic options varying from conservative procedures to more invasive surgeries. The aim of this study was to retrospectively quantify the rate of ELF after surgery for colorectal cancer, to describe its management, and to evaluate its clinical impact on early postoperative outcomes in a tertiary referral European centre. Methods: Data on all patients who underwent surgery for colorectal cancer at our institution between July 2022 and December 2024 were entered into a database. Preoperative, perioperative, and early (within 30 days) postoperative data were recorded. Results: A total of 279 patients underwent elective surgery for colorectal cancer (205 colon and 74 rectum). No postoperative deaths occurred within 30 days after surgery, and the rates of overall and major (grade ≥ 3) postoperative morbidity were 34.7% and 7.1%, respectively. The anastomotic leakage and reoperation rates were 2.8% and 5.3%, respectively. ELFs occurred in 15 patients (5.3%). In all patients, conservative treatment (based on fasting, total parenteral nutrition (TPN), and a prolonged medium-chain triglyceride (MCT) diet) was administered successfully. A recurrent ELF (after the first oral feeding resumption) occurred in four (26.6%) patients, but all were successfully treated with a conservative approach. The occurrence of an ELF prolonged the postoperative length of stay which was 12 days, a length higher than that recorded in patients without ELF. Conclusions: The occurrence of an ELF was found to be a relatively frequent complication after surgery for colorectal cancer and appears to negatively influence only the postoperative length of stay. Conservative management appeared to be a successful treatment. Full article

(This article belongs to the Special Issue Surgical Advances in Cancer Treatments: Exploring Innovative Approaches and Emerging Perspectives by the Italian College of Associate Professors of Surgery)

14 pages, 548 KiB

Open AccessArticle

Proportional Correlation Between Systemic Inflammation Response Index and Gastric Cancer Recurrence Time: A Retrospective Study

by Kyungryun In, Sunhyung Kang, Hyunseok Lee, Hyuksoo Eun, Heeseok Moon, Eaumseok Lee, Seokhyun Kim, Jaekyu Sung and Byungseok Lee

Cancers 2025, 17(9), 1415; https://doi.org/10.3390/cancers17091415 - 23 Apr 2025

Abstract

Background: Disease recurrence is the primary cause of death in patients with gastric cancer who have undergone complete surgical resection. No prognostic factors for recurrence, other than the Tumor, Node, and Metastasis stage, have been established. However, recurrence rates differ even within the [...] Read more.

Background: Disease recurrence is the primary cause of death in patients with gastric cancer who have undergone complete surgical resection. No prognostic factors for recurrence, other than the Tumor, Node, and Metastasis stage, have been established. However, recurrence rates differ even within the same Tumor, Node, and Metastasis stage. Therefore, we aimed to develop a new prognostic confidence measure for gastric cancer recurrence and demonstrate its practical utility. Methods: This was a retrospective study based on the medical records of the Chungnam National University Hospital, Republic of Korea. We enrolled patients diagnosed with stage II/III gastric cancer who underwent complete surgical resection and adjuvant chemotherapy over the past 12 years. The association between seven variables, including the systemic inflammation response index (SIRI) and gastric cancer recurrence, was analyzed. Results: A total of 296 patients were enrolled in this study. Although other factors did not exhibit significant correlations, SIRI showed a significant positive correlation with gastric cancer recurrence risk, confirmed through Cox regression testing (hazard ratio, 1.231; 95% confidence interval, 1.04‒1.45). Linear regression analysis revealed a significant association between higher SIRI values and shorter recurrence time (p = 0.044; β = −0.225). Conclusions: In this study, other than SIRI, effective prognostic factors related to gastric cancer recurrence were not verified, thus indicating SIRI as a potential independent prognostic factor. Full article

(This article belongs to the Special Issue Role of Cancer Biomarkers for Diagnosis, Prognosis and Targeted Therapy in Gastrointestinal Cancers)

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13 pages, 3436 KiB

Open AccessArticle

Predicting Visceral Pleural Invasion in Resected Lung Adenocarcinoma via Computed Tomography

by Chia-Cheng Kao, Hu-Lin Christina Wang, Mong-Wei Lin, Tung-Ming Tsai, Hsao-Hsun Hsu, Hsien-Chi Liao and Jin-Shing Chen

Cancers 2025, 17(9), 1414; https://doi.org/10.3390/cancers17091414 - 23 Apr 2025

Abstract

Background/Objectives: For thoracic surgeons, the extent of visceral pleural invasion is a crucial consideration in the surgical approach to adenocarcinoma; this invasion may influence the extent of surgical resection and predict prognosis. With advances in preoperative imaging technology, predicting visceral pleural invasion via [...] Read more.

Background/Objectives: For thoracic surgeons, the extent of visceral pleural invasion is a crucial consideration in the surgical approach to adenocarcinoma; this invasion may influence the extent of surgical resection and predict prognosis. With advances in preoperative imaging technology, predicting visceral pleural invasion via computed tomography (CT) characteristics may be feasible. The aim of this study was to evaluate the association between CT characteristics and visceral pleural invasion in patients with surgically resected lung adenocarcinoma. Methods: Patients with lung adenocarcinoma who underwent curative lung tumor resection (n = 643) were retrospectively included in this study between January 2011 and December 2015. Basic demographic CT images were analyzed by experienced thoracic surgeons and radiologists. Postoperative pathology reports were confirmed by experienced pathologists. Univariate and multivariate analyses were performed for potential prognostic factors. Results: Potential visceral pleural invasion characteristics of preoperative CT included tumor size (cm), solid part size, pleural contact of arch distance, ground glass opacity (%), tumor shape, border type, distance from visceral pleura, depth, and invasion site. In addition, solid part size, ground glass opacity (%), consolidation to tumor ratio (%), tumor shape, border type, distance from visceral pleura, and invasion site showed statistical significance for prognosis. Conclusions: Increased precision of image interpretation may provide more predictive clues to improve the identification of visceral pleural invasion before operations. The extent of surgical resection may be more accurately determined, and systemic treatment may be administered earlier for those with poor prognostic factors. Full article

(This article belongs to the Section Cancer Informatics and Big Data)

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23 pages, 1443 KiB

Open AccessSystematic Review

Assessing the Clinical Effectiveness of Radioimmunotherapy with Combined Radionuclide/Monoclonal Antibody Conjugates in Cancer Treatment: Insights from Randomised Clinical Trials

by Yifu Chen, Padam Kanta Dahal, Parvez Mosharaf, Md. Shahjalal and Rashidul Alam Mahumud

Cancers 2025, 17(9), 1413; https://doi.org/10.3390/cancers17091413 - 23 Apr 2025

Abstract

Background: Despite the development of advanced cancer therapies, achieving cancer eradication remains challenging. Radioimmunotherapy (RIT) is an innovative approach that combines radionuclides with monoclonal antibodies targeting tumour-associated antigens or those expressed by the tumour microenvironment. Over the past two decades, RIT has been [...] Read more.

Background: Despite the development of advanced cancer therapies, achieving cancer eradication remains challenging. Radioimmunotherapy (RIT) is an innovative approach that combines radionuclides with monoclonal antibodies targeting tumour-associated antigens or those expressed by the tumour microenvironment. Over the past two decades, RIT has been extensively researched, along with two RIT products—⁹⁰Y-ibritumomab tiuxetan and ¹³¹I-tositumomab. However, despite its demonstrated efficacy in non-solid tumours, RIT’s clinical use remains limited, and its effectiveness in solid tumours is inconclusive. This study aimed to analyse randomised controlled trials (RCTs) to evaluate the overall clinical effectiveness of RIT across different cancer types and its impact on treatment outcomes. Methods: A systematic search of PubMed, EMBASE, Scopus, CENTRAL, and Google Scholar was conducted from January 2000 to October 2024 in accordance with PRISMA guidelines and the PICOS framework. Studies were included if they were RCTs evaluating RIT for cancer treatment and reported treatment outcomes such as overall survival (OS), progression-free survival (PFS), disease-free survival, or time to progression (TTP). Data extraction was performed using a standardised Excel form, and study quality was assessed with the Joanna Briggs Institute Critical Appraisal Tool for RCTs. A narrative synthesis of the data was complemented by meta-analyses where feasible, particularly for progression- and survival-related endpoints. Results: Out of 2241 records identified, 20 RCTs encompassing approximately 3562 patients were included. The majority of trials focused on non-solid tumours, particularly non-Hodgkin’s lymphoma (NHL), while a smaller subset evaluated solid tumours such as lung, pancreatic, ovarian, and prostate cancers. Most non-solid tumour studies employed ⁹⁰Y-ibritumomab tiuxetan or ¹³¹I-tositumomab, targeting the CD20 antigen, whereas limited evidence exists for RIT efficacy in solid tumours. Meta-analysis of progression-related outcomes yielded a pooled hazard ratio (HR) of 0.48 (95% CI: 0.39–0.59), indicating a 52% reduction in the risk of progression. In contrast, overall survival outcomes were more variable, with a pooled OS HR of 0.80 (95% CI: 0.60–1.07). Adverse events, predominantly haematological and nonhaematological toxicities, were common yet generally reversible. The findings suggest that RIT, especially when used as part of combination regimens, significantly improves treatment outcomes in non-solid tumours but has an inconsistent effect in solid tumour settings. Conclusions: The results underscore the clinical promise of RIT in treating non-solid tumours like NHL, where combination regimens yield superior outcomes compared to monotherapy. However, the inconclusive evidence in solid tumours highlights the need for further large-scale, well-designed RCTs to define the optimal use, dosing, and patient selection for RIT in these settings. Additionally, standardisation in outcome reporting and longer follow-up periods are essential for more accurate economic and clinical assessments. Overall, RIT represents a valuable therapeutic modality, yet its integration into cancer treatment regimens should be guided by further research aimed at mitigating toxicity and optimising combination strategies. Full article

(This article belongs to the Special Issue Radioimmunotherapy, Neoadjuvant Immunotherapy, and Adjuvant Immunotherapy for Cancer)

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26 pages, 766 KiB

Open AccessReview

Treatment Sequencing in Metastatic HR+/HER2− Breast Cancer: A Delphi Consensus

by Lazar Popović, Simona Borštnar, Ivana Božović-Spasojević, Ana Cvetanović, Natalija Dedić Plavetić, Radka Kaneva, Assia Konsoulova, Erika Matos, Snježana Tomić and Eduard Vrdoljak

Cancers 2025, 17(9), 1412; https://doi.org/10.3390/cancers17091412 - 23 Apr 2025

Abstract

Background: The treatment landscape in HR+/HER2− metastatic breast cancer (mBC) is continuously evolving, with evidence on new agents and combinations published almost every year. Despite updated therapeutic guidelines, second-line (2L) selection may be challenging due to clinical factors, biomarker status, and available [...] Read more.

Background: The treatment landscape in HR+/HER2− metastatic breast cancer (mBC) is continuously evolving, with evidence on new agents and combinations published almost every year. Despite updated therapeutic guidelines, second-line (2L) selection may be challenging due to clinical factors, biomarker status, and available agents. Methods: A two-round Delphi consensus was organized in July 2024, gathering input from 10 experts in research, diagnosis, and treatment of HR+/HER2− mBC on optimal 2L and beyond choice, considering the available biomarkers and results from published clinical trials. Consensus was defined as 70% agreement or disagreement. Results: The experts considered initially a list of 39 statements, structured into the following four sections: biomarker testing; selection of 2L treatment at progression of disease on first line endocrine therapy (ET) + CDK4/6i at ≥6 months after initiation of ET for mBC; selection of 2L treatment at disease progression on ET + CDK4/6i, at <6 months after initiation of ET for mBC, whilst on ET; and selection of post-2L treatment options. After a discussion, the experts decided to remove four statements, refine ten, and include three new ones. The final list consisted of 38 statements, and consensus was achieved in 37. Conclusions: The panel recommends next-generation sequencing as the method of choice for genomic characterization at disease progression on first line. The optimal agent or treatment class is indicated depending on the presence of specific mutations; however, the panel admits that the strategy is different in clinical practice, where novel therapies might not be available or reimbursed. Full article

(This article belongs to the Section Cancer Therapy)

18 pages, 536 KiB

Open AccessArticle

Disparities in Cervical and Breast Cancer Screening Among Sexual Minority Women in Japan: A Comparative Cross-Sectional Study

by Akemi Hara, Akihiko Ozaki, Michio Murakami, Hiroaki Saito, Mika Nashimoto, Daisuke Hori, Masaharu Tsubokura, Kenji Gonda, Masahiro Wada, Kazunoshin Tachibana, Tohru Ohtake and Takahiro Tabuchi

Cancers 2025, 17(9), 1411; https://doi.org/10.3390/cancers17091411 - 23 Apr 2025

Abstract

Objectives: While health disparities affecting sexual minority women are well-documented globally, little is known about cancer screening behaviors among sexual minority women in Japan. Following our previous study on breast cancer screening, this study examined cervical cancer screening participation patterns and compared [...] Read more.

Objectives: While health disparities affecting sexual minority women are well-documented globally, little is known about cancer screening behaviors among sexual minority women in Japan. Following our previous study on breast cancer screening, this study examined cervical cancer screening participation patterns and compared screening behaviors between both cancer types among sexual minority women in Japan. Methods: We analyzed data from 13,730 individuals with female sex assigned at birth who participated in a nationwide online survey between September and November 2023. Multinomial logistic regression was used to examine factors associated with screening participation, comparing sexual minority women (n = 2685) and women who are not part of a sexual minority (n = 11,045). Among participants aged 40 and above (n = 8933), we compared participation patterns between cervical and breast cancer screenings. Results: Sexual minority women showed significantly lower cervical cancer screening rates compared to women who are not part of a sexual minority (38.7% vs. 45.6%, p < 0.001), with a wider disparity than observed in breast cancer screening (43.4% vs. 45.9%, p < 0.001). Among those aged 40 and above, sexual minority women were more likely to skip both screenings (35.0% vs. 27.2%) and less likely to participate in both (55.0% vs. 62.6%). Additionally, our analysis revealed that participants with a current mental disorder (i.e., those reporting ongoing mental health issues) were more likely to intend to undergo cervical cancer screening (aOR = 1.39, 95% CI = 1.15–1.67, p = 0.001). In contrast, among bisexual participants and those classified as having “other” mental health conditions—defined as a history of mental health issues without current symptoms—exhibited significantly lower odds of being screened (aOR = 0.31, 95% CI = 0.11–0.82, p = 0.02). Conclusions: Significant disparities exist in cancer screening participation among sexual minority women in Japan, with more pronounced differences in cervical cancer screening compared to breast cancer screening. These findings highlight the need for targeted interventions addressing the unique barriers to gynecological care among sexual minority women. Full article

(This article belongs to the Special Issue Disparities in Cancer Prevention, Screening, Diagnosis and Management)

31 pages, 679 KiB

Open AccessReview

Physical Activity and Cancer Incidence and Mortality: Current Evidence and Biological Mechanisms

by Joanna Kruk, Basil Hassan Aboul-Enein, Marta Ewelina Gołębiewska, Ewa Duchnik, Urszula Czerniak and Mariola Marchlewicz

Cancers 2025, 17(9), 1410; https://doi.org/10.3390/cancers17091410 - 23 Apr 2025

Abstract

Objectives: There is strong evidence that not enough physical activity is among the most critical risk factors for cancer disease and premature mortality. The literature on the benefits of regular physical activity regarding cancer disease has grown in the last decades. This review [...] Read more.

Objectives: There is strong evidence that not enough physical activity is among the most critical risk factors for cancer disease and premature mortality. The literature on the benefits of regular physical activity regarding cancer disease has grown in the last decades. This review aimed to present the current findings on the effect of prediagnosis physical activity on cancer incidence and mortality published between January 2019 and October 2024; this study summarizes the previous evidence, as well as the literature underlying biological mechanisms operating in the exercise–cancer relationship. The review also highlights gaps in the existing research and identifies future research directions. Methods: Medline/PubMed, ScienceDirect, and Google Scholar were searched with the search terms “physical activity” and “physical exercise” in conjunction with the MeSH terms for “cancer” and “carcinoma”. Primary, review, and meta-analysis studies published in English were included if they reported a measure of the effect size of prediagnosis physical activity on cancer incidence and/or cancer mortality. Results: Evidence from 37 observational studies and 10 reviews were included in this systematic review; 22 studies reported the effect of physical activity on cancer incidence, and 15 studies on cancer mortality. Of the 37 included observational studies, 19 confirmed the previous evidence that physical activity significantly decreased all-cancer-combined and cancer-specific site incidences, and 10 studies focused on cancer mortality. However, the molecular mechanisms involved in this process require future studies. The most convincing evidence maintains the effects of physical activity on body weight and fat, insulin resistance, sex hormones, regulation of redox homeostasis, enhancing the antioxidant defense system, and reducing oxidative stress. Conclusions: These data demonstrate substantial prevention against several cancer incidences and mortality among patients who performed regular physical activity, of which dose meets at least the WHO’s guidelines. Further prospective cohort studies and long-term RCT studies are warranted to address a safe and personalized activity dose for cancer-site prevention, identify more precisely the biological mechanisms operating in the physical activity–cancer relationship, and promote the benefits of being physically active. Full article

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

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15 pages, 974 KiB

Open AccessArticle

Preoperative and Postoperative Change in Patient-Reported Health-Related Quality of Life Outcomes in Breast Cancer Surgery Patients Across Surgical Modalities: A Prospective Study

by Claire Liu, Aidan Beresford, Maria Saleeb, Guiping Liu, Trafford Crump, Rebecca Warburton, Jin-Si Pao, Carol K. Dingee, Amy Bazzarelli, Jason M. Sutherland and Elaine C. McKevitt

Cancers 2025, 17(9), 1409; https://doi.org/10.3390/cancers17091409 - 23 Apr 2025

Abstract

Background: This study compared the change in pre- and postoperative health-related quality of life (HRQoL) among breast cancer patients undergoing breast-conserving surgery (BCS), total mastectomy no reconstruction (TMNR), and total mastectomy immediate breast reconstruction (MIBR). Patient factors associated with postoperative anxiety and [...] Read more.

Background: This study compared the change in pre- and postoperative health-related quality of life (HRQoL) among breast cancer patients undergoing breast-conserving surgery (BCS), total mastectomy no reconstruction (TMNR), and total mastectomy immediate breast reconstruction (MIBR). Patient factors associated with postoperative anxiety and depression were also identified. Methods: This prospective cohort study enrolled breast cancer patients between September 2017 and August 2020. HRQoL changes from preoperative to six months postoperative were compared using patient-reported outcome tools assessing anxiety, depression, pain, perceived health, breast satisfaction, psychosocial, physical, and sexual well-being and analyzed with ANOVA and linear regression. Results: A total of 471 patients completed preoperative and postoperative surveys (BCS: 313, TMNR: 60, MIBR: 98). Postoperative anxiety decreased across all modalities, with MIBR showing the greatest reduction (p = 0.03), though still exhibiting the highest postoperative anxiety (p = 0.05). Depression and perceived health scores showed no significant difference in change across modalities (p = 0.15, p = 0.48). MIBR patients showed the greatest increase in pain (p = 0.05) and the highest postoperative pain scores (p = 0.04). All three modalities showed a clinically significant decline in physical and sexual well-being. TMNR and MIBR had additional reductions in breast satisfaction, with TMNR also showing a decline in psychosocial well-being. Absolute postoperative scores for breast satisfaction, psychosocial, physical, and sexual well-being remained highest in BCS compared to TMNR and MIBR (p < 0.01, for each domain). In multivariable regression analysis, postoperative depression and anxiety scores did not differ between surgical modalities, but younger age was significantly associated with higher postoperative depression, pain and anxiety (p < 0.01), and adjuvant chemotherapy with higher postoperative depression (p < 0.01). Conclusions: BCS may have better overall HRQoL outcomes, specifically in breast satisfaction, psychosocial, physical, and sexual well-being, compared to TMNR and MIBR. Additionally, younger age, rather than surgical modality, was found to be associated with higher postoperative depression, pain, and anxiety scores. Full article

(This article belongs to the Special Issue New Developments in Breast Cancer Surgery, Risk, and Related Quality of Life)

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32 pages, 1157 KiB

Open AccessReview

Advancing Cancer Treatment: A Review of Immune Checkpoint Inhibitors and Combination Strategies

by Valencia Mc Neil and Seung Won Lee

Cancers 2025, 17(9), 1408; https://doi.org/10.3390/cancers17091408 - 23 Apr 2025

Abstract

A groundbreaking milestone in oncology has been the recognition and targeted elimination of malignant cells through cancer immunotherapy, which harnesses the body’s immune system to attack cancer [...] Full article

(This article belongs to the Section Cancer Therapy)

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26 pages, 8380 KiB

Open AccessArticle

Roles of Annexin A1 Expression in Small Cell Lung Cancer

by Ágnes Paál, David Dora, Ákos Takács, Christopher Rivard, Shivaun Lueke Pickard, Fred R. Hirsch, Brigitta Roskó, Peter Kiraly, Péter Ferdinandy, Zoltán V. Varga, Zoltan Lohinai and Anikó Görbe

Cancers 2025, 17(9), 1407; https://doi.org/10.3390/cancers17091407 - 23 Apr 2025

Abstract

Background/Objectives: Small cell lung cancer (SCLC) is one of the malignancies with the worst prognosis, and there have been no major breakthroughs in its treatment for a long time. The majority of patients are diagnosed at the extensive stage, where the only option [...] Read more.

Background/Objectives: Small cell lung cancer (SCLC) is one of the malignancies with the worst prognosis, and there have been no major breakthroughs in its treatment for a long time. The majority of patients are diagnosed at the extensive stage, where the only option is chemotherapy, and even the addition of immune checkpoint inhibitors results in only modest benefits. The characterization of the molecular mechanisms behind therapy resistance has relevance in finding novel therapeutic approaches. Previous studies showed the possibility of annexin A1’s (ANXA1) involvement in the immunosuppressive tumor microenvironment in SCLC, and there are studies showing the direct effects of ANXA1 modulation on cancer cell aggressiveness. Methods: We aimed to characterize the roles of ANXA1 expression using publicly available transcriptomic data, the RNA-seq-based predictive algorithms EPIC and ESTIMATE, and immunohistochemistry on patient samples. For the in vitro studies, we silenced ANXA1 expression with short hairpin RNA in three SCLC cell lines, measured the growth rate with the trypan blue exclusion assay, assessed the chemosensitivity to cisplatin and etoposide with the Presto Blue^TM viability assay, and performed Western blots to assess changes in the levels of metabolic and mesenchymal markers and transcriptional drivers. Results: ANXA1-high tumors are associated with significantly increased immune infiltrates, stromality, and tumor-associated macrophages (TAMs). The ANXA1 protein is expressed on tumor cells and TAMs at the tissue level. ANXA1 silencing in H841 cells did not affect the growth rate; in SW1271 cells, shANXA1 cells grew significantly slower than shCTRL cells. Meanwhile, in H1048 cells, proliferation was significantly faster. Despite the different growth rates of the tested cell lines, ANXA1 silencing decreased the chemosensitivity to both cisplatin and etoposide in all three cell lines. Gene expression changes in mesenchymal markers, metabolic markers, dominant transcriptional drivers, and immune-relevant molecules were also characterized. Conclusions: This is the first comprehensive characterization of ANXA1 in SCLC to reveal its role in the tumor’s cell biology and the TME, aiming to boost further research in the field. Full article

(This article belongs to the Special Issue Lung Cancer: Molecular Pathways, Current Therapies and New Targeted Treatments)

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12 pages, 2609 KiB

Open AccessArticle

VEGF-C and Lymphatic Vessel Density in Tumor Tissue of Gastric Cancer: Correlations with Pathoclinical Features and Prognosis

by Mariusz Szajewski, Maciej Ciesielski, Rafał Pęksa, Piotr Kurek, Michał Stańczak, Jakub Walczak, Jacek Zieliński and Wiesław Janusz Kruszewski

Cancers 2025, 17(9), 1406; https://doi.org/10.3390/cancers17091406 - 23 Apr 2025

Abstract

Objectives: The objective of this study was to assess the relationship of VEGF-C and LVD with pathoclinical factors of potential prognostic value and with the survival time of gastric cancer patients. Materials and methods: A total of 103 radically operated patients for gastric [...] Read more.

Objectives: The objective of this study was to assess the relationship of VEGF-C and LVD with pathoclinical factors of potential prognostic value and with the survival time of gastric cancer patients. Materials and methods: A total of 103 radically operated patients for gastric cancer who did not undergo neoadjuvant therapy were included in this study. The minimum follow-up period after surgery was 61 months. VEGF-C and lymphatic vessels were immunohistochemically determined using antibodies, including VEGF-C (c-20) sc 1881-Goat Polyclonal IgG (Santa Cruz Biotechnology) and Podoplanin D2-40 Mouse Monoclonal Antibody (ROCHE). The relationship between VEGF-C expression in gastric adenocarcinoma cells and the density of lymphatic vessels at the periphery of the primary tumor was assessed, along with the relationships of VEGF-C and LVD with selected pathoclinical parameters of gastric cancer and prognosis. Results: VEGF-C overexpression was associated with increased LVD (Mann–Whitney U test, p = 0.03) and the Lauren intestinal type of cancer (Pearson’s chi-square test, p < 0.001). Increased LVD was more often associated with cancers located beyond the cardia (Mann–Whitney U test, p = 0.04). We did not demonstrate an association of VEGF-C or LVD with OS or with prognostic features, such as pT, pN, or pTNM staging. However, in the Lauren intestinal type of cancer, VEGF-C overexpression correlated with shorter OS (log-rank, p = 0.01) and, at the level of p = 0.05 in multivariate analysis, it had an independent negative prognostic value. Conclusions: Peritumoral overexpression of VEGF-C in primary gastric cancer tumors is associated with increased LVD. The Lauren intestinal type of cancer is associated with VEGF-C overexpression. The overexpression of VEGF-C in intestinal-type gastric cancer is associated with worse prognosis. Full article

(This article belongs to the Special Issue Gastric Cancer Surgery: Gastrectomy, Risk, and Related Prognosis)

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15 pages, 2711 KiB

Open AccessArticle

Proposed Refinement of 2022 European LeukemiaNet Adverse-Risk Group of AML Patients Using a Real-World Cohort

by Collins Wangulu, Davidson Zhao, Qianghua Zhou, Cuihong Wei, Rajat Kumar, Aaron Schimmer and Hong Chang

Cancers 2025, 17(9), 1405; https://doi.org/10.3390/cancers17091405 - 23 Apr 2025

Abstract

Background/Objectives: The 2022 European LeukemiaNet (ELN 2022) is a widely used genotypic risk classification tool for the treatment and prognostication of acute myeloid leukemia (AML) patients. Our study evaluates its effectiveness in categorizing adverse-risk AML patients on standard therapy based on their overall [...] Read more.

Background/Objectives: The 2022 European LeukemiaNet (ELN 2022) is a widely used genotypic risk classification tool for the treatment and prognostication of acute myeloid leukemia (AML) patients. Our study evaluates its effectiveness in categorizing adverse-risk AML patients on standard therapy based on their overall survival (OS). Methods: We conducted a retrospective study involving 256 AML patients. Results: Those in the ELN 2022 adverse-risk group had the shortest OS (p < 0.0001) and were predominantly characterized by myelodysplasia-related (MR) mutations, complex karyotype (CK), monosomal karyotype (MK), and TP53 mutation (TP53 Mut). Subclassification and analysis of this adverse-risk group based on the TP53 Mut status revealed a significantly shorter OS compared to the adverse TP53 wild-type (TP53 WT) counterparts (p = 0.0036). We propose refining the ELN 2022 adverse-risk group into two categories, adverse TP53 Mut and adverse TP53 WT groups, to represent adverse- and ultra-adverse-risk groups, respectively. We used an external validation dataset to confirm our findings. Conclusions: This refinement allows for a more accurate classification of these adverse-risk patients based on their clinical outcomes. Full article

(This article belongs to the Special Issue New Insights of Hematology in Cancer)

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16 pages, 1261 KiB

Open AccessArticle

Predictors in Optic Pathway Gliomas in Neurofibromatosis Type 1: A Single Center Study

by Agata Marjańska, Jagoda Styczyńska, Agnieszka Jatczak-Gaca, Joanna Stachura, Michał Marjański and Jan Styczyński

Cancers 2025, 17(9), 1404; https://doi.org/10.3390/cancers17091404 - 23 Apr 2025

Abstract

Background/Aim: Among NF1-dependent tumors, the most common are optic pathway gliomas (OPGs). The objective of this study was the retrospective analysis of the course, indications for treatment, and effects of therapy for NF1-OPGs. Patients and Methods: We analyzed demographics, clinical and genetic data, [...] Read more.

Background/Aim: Among NF1-dependent tumors, the most common are optic pathway gliomas (OPGs). The objective of this study was the retrospective analysis of the course, indications for treatment, and effects of therapy for NF1-OPGs. Patients and Methods: We analyzed demographics, clinical and genetic data, imaging and ophthalmological parameters, their impact on therapeutic decisions, and the effectiveness of the therapy in 92 patients. Results: OPGs were unilateral in 55.4% of patients and bilateral in 44.6%. Post-contrast enhancement in MRI was observed in 67.4%. Oncological treatment was required in 16.3% of patients with median age 3.8 years. Factors significant in multivariate analysis contributing to the need of oncological treatment were: amblyopia and proptosis. Factors contributing to amblyopia were: strabismus, proptosis, co-occurrence of epilepsy, bilateral OPGs, and thickness of the optic nerve ≥ 8 mm. The first line of oncological treatment included vincristine + carboplatin or monotherapy with vinblastine. The use of subsequent lines of oncological treatment was necessary in 46.7% patients. Conclusions: The following conclusions, suggest modification of the approach in the management of patients with NF1-OPG, summarize the presented study: (1) perform the first MRI after the age of 1 year, (2) reduce the frequency of follow-up scans in the first year of observation in patients with isolated involvement of intraocular and/or intraorbital segments of the optic nerve, (3) refrain from administering contrast during control MRI examinations of the orbits after OPG diagnosis; (4) in patients with co-occurring psychomotor delay or treated with antiepileptic drugs, do not make decisions about oncological therapy when visual acuity deterioration is observed, without progression in optical coherence tomography (OCT), visual evoked potentials (VEP), and MRI. Full article

(This article belongs to the Section Pediatric Oncology)

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16 pages, 1308 KiB

Open AccessReview

Current Treatment of Uveal Melanoma

by Katie Hanratty, Gráinne Finegan, Keith D. Rochfort and Susan Kennedy

Cancers 2025, 17(9), 1403; https://doi.org/10.3390/cancers17091403 - 23 Apr 2025

Abstract

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults worldwide [...] Full article

(This article belongs to the Section Cancer Therapy)

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15 pages, 688 KiB

Open AccessReview

Targeting Autophagy for Pituitary Tumors

by Evan Yin, Motoyasu Satou and Toru Tateno

Cancers 2025, 17(9), 1402; https://doi.org/10.3390/cancers17091402 - 23 Apr 2025

Abstract

Pituitary tumors, arising from the pituitary gland, can be classified as functioning or non-functioning based on their hormone production. Previous studies demonstrated that impairment of cellular processes, such as autophagy, a crucial cellular recycling mechanism, has been implicated in pituitary tumorigenesis and hormone [...] Read more.

Pituitary tumors, arising from the pituitary gland, can be classified as functioning or non-functioning based on their hormone production. Previous studies demonstrated that impairment of cellular processes, such as autophagy, a crucial cellular recycling mechanism, has been implicated in pituitary tumorigenesis and hormone dysregulation. This review comprehensively examines the intricate relationship between autophagy and pituitary tumors. We explore the multifaceted role of autophagy in cancer, highlighting its dual nature as both a tumor suppressor and a promoter depending on the context. We also discuss the specific mechanisms of autophagy, including macroautophagy, mitophagy, crinophagy, and their relevance to pituitary tumorigenesis and hormone regulation. Furthermore, we analyze the current literature regarding the impact of various therapeutic interventions in pituitary tumor cells, with both autophagy-promoting and autophagy-inhibiting strategies. We address the challenges in interpreting autophagy activity and its complex interplay with hormone production. Current evidence suggests the potential of targeting autophagy as a therapeutic approach for pituitary tumors, emphasizing further research and clinical trials to determine the optimal strategy for individual patients and improve long-term outcomes. Full article

(This article belongs to the Special Issue The Role of Apoptosis and Autophagy in Cancer)

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16 pages, 265 KiB

Open AccessReview

The Role of Robot-Assisted, Imaging-Guided Surgery in Prostate Cancer Patients

by Leonardo Quarta, Donato Cannoletta, Francesco Pellegrino, Francesco Barletta, Simone Scuderi, Elio Mazzone, Armando Stabile, Francesco Montorsi, Giorgio Gandaglia and Alberto Briganti

Cancers 2025, 17(9), 1401; https://doi.org/10.3390/cancers17091401 - 23 Apr 2025

Abstract

Emerging imaging-guided technologies, such as prostate-specific membrane antigen radioguided surgery (PSMA-RGS) and augmented reality (AR), could enhance the precision and efficacy of robot-assisted prostate cancer (PCa) surgical approaches, maximizing the surgeons’ ability to remove all cancer sites and thus patients’ outcomes. Sentinel node [...] Read more.

Emerging imaging-guided technologies, such as prostate-specific membrane antigen radioguided surgery (PSMA-RGS) and augmented reality (AR), could enhance the precision and efficacy of robot-assisted prostate cancer (PCa) surgical approaches, maximizing the surgeons’ ability to remove all cancer sites and thus patients’ outcomes. Sentinel node biopsy (SNB) represents an imaging-guided technique that could enhance nodal staging accuracy by leveraging lymphatic mapping with tracers. PSMA-RGS uses radiolabeled tracers with the aim to improve intraoperative lymph node metastases (LNMs) detection. Several studies demonstrated its feasibility and safety, with promising accuracy in nodal staging during robot-assisted radical prostatectomy (RARP) and in recurrence setting during salvage lymph node dissection (sLND) in patients who experience biochemical recurrence (BCR) after primary treatment and have positive PSMA positron emission tomography (PET). Near-infrared PSMA tracers, such as OTL78 and IS-002, have shown potential in intraoperative fluorescence-guided surgery, improving positive surgical margins (PSMs) and LNMs identification. Finally, augmented reality (AR), which integrates preoperative imaging (e.g., multiparametric magnetic resonance imaging [mpMRI] of the prostate and computed tomography [CT]) onto the surgical field, can provide a real-time visualization of anatomical structures through the creation of three-dimensional (3D) models. These technologies may assist surgeons during intraoperative procedures, thus optimizing the balance between oncological control and functional outcomes. However, challenges remain in standardizing these tools and assessing their impact on long-term PCa control. Overall, these advancements represent a paradigm shift toward personalized and precise surgical approaches, emphasizing the integration of innovative strategies to improve outcomes of PCa patients. Full article

(This article belongs to the Special Issue The Role of Robot‐Assisted Radical Prostatectomy in Prostate Cancer)

1 pages, 125 KiB

Open AccessExpression of Concern

Expression of Concern: De Bari et al. Could 18-FDG PET-CT Radiomic Features Predict the Locoregional Progression-Free Survival in Inoperable or Unresectable Oesophageal Cancer? Cancers 2022, 14, 4043

by Cancers Editorial Office

Cancers 2025, 17(9), 1400; https://doi.org/10.3390/cancers17091400 - 23 Apr 2025

Abstract

In this notice, the Cancers Editorial Office alerts readers to concerns related to this article [...] Full article

13 pages, 620 KiB

Open AccessArticle

Outcomes for Medicaid Patients with Colorectal Cancer Are Improved in Affluent Neighborhoods, but Disparities Persist

by Kaelyn C. Cummins, Mohamad El Moheb, Chengli Shen, Susan J. Kim, Russell Witt, Samantha M. Ruff and Allan Tsung

Cancers 2025, 17(9), 1399; https://doi.org/10.3390/cancers17091399 - 22 Apr 2025

Abstract

Background: Socioeconomic status (SES) significantly influences outcomes in colorectal cancer (CRC) patients, with those from low-SES backgrounds facing worse prognoses. However, living in an affluent neighborhood may mitigate some of these disparities through environmental advantages. This study investigates whether Medicaid-insured CRC patients, as [...] Read more.

Background: Socioeconomic status (SES) significantly influences outcomes in colorectal cancer (CRC) patients, with those from low-SES backgrounds facing worse prognoses. However, living in an affluent neighborhood may mitigate some of these disparities through environmental advantages. This study investigates whether Medicaid-insured CRC patients, as a proxy for low individual SES, experience better outcomes when residing in high-SES neighborhoods. Methods: Using the National Cancer Database, we examined Medicaid CRC patients, stratifying them by neighborhood SES indicators: median household income and education level. Patients in the highest and lowest quartiles of income and education were compared. Medicaid patients from the highest-SES neighborhoods were compared to the general population. Multivariable regression models analyzed 30- and 90-day postoperative mortality, overall survival (OS), and time from diagnosis to treatment initiation and surgery. Results: CRC patients in high-income neighborhoods began treatment earlier (coefficient −1.847, p = 0.015) and exhibited improved OS (HR 0.810, p < 0.001) compared to those in low-income neighborhoods, irrespective of education level. Similarly, patients in high-education neighborhoods started treatment sooner (coefficient −3.926, p < 0.001) and had better OS (HR 0.897, p < 0.001). No differences were observed in time to surgery or postoperative mortality. Despite these advantages, Medicaid patients in high-income (HR 1.130, p < 0.001) and high-education (HR 1.209, p = 0.002) areas still had worse OS compared to non-Medicaid patients. Conclusions: Higher neighborhood SES is associated with a significant survival benefit for Medicaid CRC patients, but these patients still lag behind their non-Medicaid counterparts. Understanding the mechanisms by which neighborhood SES influences cancer outcomes could inform targeted interventions to close the survival gap. Full article

(This article belongs to the Special Issue Impact of Social Determinants on Cancer Care)

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24 pages, 941 KiB

Open AccessSystematic Review

Hyperthyroidism Associated with Gestational Trophoblastic Neoplasia: Systematic Literature Review and Pathways Analysis

by Alina Badlaeva, Anna Tregubova, Aleksandra Asaturova, Beatrice Melli, Vincenza Ylenia Cusenza and Andrea Palicelli

Cancers 2025, 17(9), 1398; https://doi.org/10.3390/cancers17091398 - 22 Apr 2025

Abstract

Background/Objectives: Gestational trophoblastic disease (GTD) is a group of disorders including complete, partial, and invasive/metastatic hydatidiform moles, as well as gestational trophoblastic neoplasia (GTN) (choriocarcinoma; placental site trophoblastic tumor, PSTT; epithelioid trophoblastic tumor, ETT; or mixed forms). These entities are characterized by [...] Read more.

Background/Objectives: Gestational trophoblastic disease (GTD) is a group of disorders including complete, partial, and invasive/metastatic hydatidiform moles, as well as gestational trophoblastic neoplasia (GTN) (choriocarcinoma; placental site trophoblastic tumor, PSTT; epithelioid trophoblastic tumor, ETT; or mixed forms). These entities are characterized by increased trophoblast proliferation, rarely complicated by hyperthyroidism. Methods: Our systematic literature review (PRISMA guidelines; PubMed, Web of Science, and Scopus databases) searched for histologically confirmed cases of GTN associated with clinical or subclinical hyperthyroidism. We described the clinical–pathologic features and the pathways of hyperthyroidism in GTD. Results: We identified just 32 choriocarcinomas and one PSTT; other non-histologically confirmed cases could have been identified, as some patients received a clinical diagnosis based on serum human chorionic gonadotropin (hCG) levels and imagining data and were treated accordingly. As regards choriocarcinomas, patients’ age range was 15–45 (mean 27) years. Metastases involved the lungs (53%), brain (25%), and liver (19%) (less frequently, the kidneys, spleen, ovaries, vagina, pelvis/abdomen, or thyroid). The time to recurrence range was 1–36 (mean 12) months. On follow-up, 10 patients (32%) were alive with disease and 6 (19%) showed no evidence of disease, while most of the women (15 cases, 48%) died of disease. The hCG level range was 10,000–3,058,000,000 (mean 128,957,613) IU/L. At least some symptoms and/or signs of hyperthyroidism were evident with variable intensity in most cases and significantly improved within 2–3 weeks after treatment. Conclusions: Increased trophoblast proliferation could stimulate thyroid function via increasing the half-life of thyroxine-binding globulin. Secondly, increased hCG demonstrates cross-reactivity with the thyroid-stimulating hormone due to similar α-subunits. Moreover, basic isoforms of hCG may facilitate thyrotropic activity. Full article

(This article belongs to the Special Issue Rare Gynecological Cancers)

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11 pages, 784 KiB

Open AccessArticle

Influence of Age on Treatment and Prognosis in Ovarian Cancer Patients

by Gemma Mancebo, Josep Maria Sole-Sedeno, Berta Fabregó, Giovanna Pinto, Adrián Vizoso, Marta Alvarez, Rosa Ana Sabaté-Garcia and Ester Miralpeix

Cancers 2025, 17(9), 1397; https://doi.org/10.3390/cancers17091397 - 22 Apr 2025

Abstract

Background: Ovarian cancer, particularly in advanced stages, requires cytoreductive surgery followed by chemotherapy. A significant proportion of patients are elderly, yet older women are often treated with non-standard regimens despite a lack of consistent evidence linking age to prognosis. The aim of [...] Read more.

Background: Ovarian cancer, particularly in advanced stages, requires cytoreductive surgery followed by chemotherapy. A significant proportion of patients are elderly, yet older women are often treated with non-standard regimens despite a lack of consistent evidence linking age to prognosis. The aim of this study is to assess age-specific differences in treatment and survival outcomes for ovarian cancer in women aged 70 years or older. Methods: This retrospective study included ovarian cancer patients treated at the Hospital del Mar, Barcelona, between 2016 and 2022. Patients were stratified into two groups: <70 and ≥70 years. Clinical and pathological data were analyzed, and hazard ratios (HR) for overall survival (OS) and disease-free survival (DFS) were calculated using Cox proportional hazards regression models. Multivariate analysis was performed to compare outcomes. Results: A total of 110 patients were included (73 <70 years, 37 ≥70 years). Among the older group, 80.5% were diagnosed at advanced stages (III–IV), compared to 63% in the younger group (p = 0.012). Patients aged ≥70 were more likely to undergo interval surgery (p = 0.053) and receive non-standard treatment (p = 0.023). Complete cytoreduction was achieved in 95.8% of younger patients versus 81.3% of older patients (p = 0.024). Age ≥70 did not significantly impact DFS (p = 0.091), but OS was significantly worse in the older group (44.4% vs. 67.2%, p = 0.014). Conclusions: Older women (≥70 years) with ovarian cancer are more likely to be diagnosed at advanced stages, receive non-standard treatment, and achieve suboptimal cytoreduction compared to younger patients. While DFS was similar across age groups, older age was associated with worse OS, highlighting the need for age-tailored treatment strategies. Full article

(This article belongs to the Special Issue Women’s Health and Gynaecological Cancers: From Nutrition and Environmental Factors to Novel Diagnostics and Therapies)

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13 pages, 1159 KiB

Open AccessArticle

Risk Factors for Intestinal and Extraintestinal Cancers in Inflammatory Bowel Disease: A Retrospective Single-Center Cohort Study

by Rosa Rosania, Maximilian Nord, Florian G. Scurt, Anke Lux, Verena Keitel, Ulrike von Arnim and Marino Venerito

Cancers 2025, 17(9), 1396; https://doi.org/10.3390/cancers17091396 - 22 Apr 2025

Abstract

Background/Objectives: Patients with inflammatory bowel disease (IBD) face an increased risk of developing intestinal and extraintestinal cancers. This retrospective single-center study aimed to quantify cancer risk and identify potential risk factors associated with cancer in IBD patients. Methods: The epidemiological data, [...] Read more.

Background/Objectives: Patients with inflammatory bowel disease (IBD) face an increased risk of developing intestinal and extraintestinal cancers. This retrospective single-center study aimed to quantify cancer risk and identify potential risk factors associated with cancer in IBD patients. Methods: The epidemiological data, disease characteristics, treatment regimens, and occurrences of cancer following IBD diagnosis were collected between January 2021 and February 2022. Hazard ratios (HRs) and standardized incidence ratios (SIRs) were estimated. Results: 560 IBD patients were included; 37 patients developed cancer, with 5 patients developing two distinct cancers, resulting in 42 cancers overall. This translated into a twofold increased risk of developing any cancer compared to the general population (SIR 1.94, 95% CI 1.4–2.6). Colorectal (CRC, 29%), skin (19%), and breast cancer (17%) were the most common malignancies. Female patients showed an increased risk for all cancers (SIR 3.1, 95% CI 2.06–4.3), melanoma (SIR 5.6, 95% CI 1.14–16.2), and CRC (SIR 7.5, 95% CI 3–15.4). Conversely, male patients exhibited a significantly increased risk of lymphoma (SIR 26.2, 95% CI 3.2–95.7). Young age at IBD diagnosis and the use of immunomodulators, whether as monotherapy or in combination with biologics, were associated with an increased risk of cancer. Conclusions: The risk of CRC and lymphoma in IBD patients may be higher than previously reported, potentially due to the increasing use of combination therapy. Cancer risk in IBD should be regularly assessed and personalized throughout the disease course. Full article

(This article belongs to the Special Issue Clinical Epidemiology and Risk Prediction for Gastrointestinal Cancers)

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19 pages, 2900 KiB

Open AccessArticle

Analysis of Genotype and Expression of FTO and ALKBH5 in a MENA-Region Renal Cell Carcinoma Cohort

by Muna Abdalla Alhammadi, Burcu Yener Ilce, Poorna Manasa Bhamidimarri, Amal Bouzid, Nival Ali, Reem Sami Alhamidi, Alaa Mohamed Hamad, Mona Mahfood, Abdelaziz Tlili, Iman M. Talaat and Rifat Hamoudi

Cancers 2025, 17(9), 1395; https://doi.org/10.3390/cancers17091395 - 22 Apr 2025

Abstract

Background/Objectives: RNA-modifying proteins play a crucial role in the progression of cancer. The fat mass and obesity-associated protein (FTO) and alkB homolog 5 RNA demethylase (ALKBH5) are RNA-demethylating proteins that have contrasting effects in renal cell carcinoma (RCC) among different populations. This [...] Read more.

Background/Objectives: RNA-modifying proteins play a crucial role in the progression of cancer. The fat mass and obesity-associated protein (FTO) and alkB homolog 5 RNA demethylase (ALKBH5) are RNA-demethylating proteins that have contrasting effects in renal cell carcinoma (RCC) among different populations. This research investigates the genotype and expression levels of FTO and ALKBH5 in RCC patients from the Middle East and Northern Africa (MENA) region. Methods: Formalin-fixed paraffin-embedded samples from the kidney biopsies of RCC patients and controls were examined using targeted DNA sequencing, whole transcriptome profiling, and immunohistochemistry. Results: Our findings show that the rs11075995T variant in FTO is associated with a heightened risk of clear-cell RCC (ccRCC). ALKBH5 and FTO protein expression were significantly lower in ccRCC and chromophobe RCC (chRCC) patients but not in papillary RCC (pRCC) patients. In ccRCC, transcriptomic data revealed a significant downregulation of FTO (log₂FC = −5.2, q < 0.001) and ALKBH5 (log₂FC = −4.7, q < 0.001) compared to controls. A significant negative correlation was found in ccRCC between FTO expression and T allele frequency in rs11075995, suggesting that FTO expression is affected. Conclusions: This is the first demonstration of the association of the dysregulated expression of FTO and ALKBH5 in ccRCC and chRCC patients from the MENA region. FTO variant rs11075995T increased the risk of ccRCC and was negatively associated with FTO protein expression. Full article

(This article belongs to the Section Molecular Cancer Biology)

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14 pages, 876 KiB

Open AccessArticle

Robot-Assisted Radical Nephroureterectomy: A Safe and Effective Option for Upper Tract Urothelial Carcinoma, Especially for Novice Surgeons

by Chia-Lun Chang, Chung-You Tsai, Pai-Yu Cheng, Wen-Jeng Wu and Yao-Chou Tsai

Cancers 2025, 17(9), 1394; https://doi.org/10.3390/cancers17091394 - 22 Apr 2025

Abstract

Background: Radical nephroureterectomy (RNU) is the standard treatment for upper tract urothelial carcinoma (UTUC). Minimally invasive techniques like robotic (RARNU) and laparoscopic (LRNU) RNU offer potential benefits over open surgery, but their comparative oncologic outcomes are debated. Methods: This retrospective, multicenter study analyzed [...] Read more.

Background: Radical nephroureterectomy (RNU) is the standard treatment for upper tract urothelial carcinoma (UTUC). Minimally invasive techniques like robotic (RARNU) and laparoscopic (LRNU) RNU offer potential benefits over open surgery, but their comparative oncologic outcomes are debated. Methods: This retrospective, multicenter study analyzed 2037 Taiwanese patients undergoing RNU between 2010 and 2022. Missing data was addressed using multiple imputations. Overlap weighting was applied to balance patient characteristics between the RARNU and LRNU groups. Survival outcomes were compared using Kaplan-Meier analysis and Cox regression. Results: After excluding the missing data, 405 patients underwent RARNU, and 1262 underwent LRNU. After adjusting for baseline differences, both groups showed comparable rates of surgical complications, residual tumor, UTUC-related mortality, and disease recurrence. The median follow-up was similar (52.4 vs. 51.6 months, p = 0.91). Using Kaplan-Meier survival curve analysis, overall survival, cancer-specific survival, and disease-free survival were similar between the two groups. Conclusions: This study shows that RARNU for UTUC has comparable oncological and perioperative outcomes to pure LRNU. RARNU may be easier for surgeons to adopt, particularly those with limited laparoscopic experience. Full article

(This article belongs to the Special Issue Urologic Cancer: Endoscopic, Laparoscopic, and Robot-Assisted Surgery Management)

17 pages, 1515 KiB

Open AccessArticle

Feasibility and Effects of Implementing Multimodal Prehabilitation Before Cytoreductive Surgery in Patients with Ovarian Cancer: The Gynofit Multicenter Study

by Stella van der Graaff, Tessa A. M. Backhuijs, Frank P. de Kort, Elize W. Lockhorst, Huberdina P. M. Smedts, Jennifer M. J. Schreinemakers, Gatske M. Nieuwenhuyzen-de Boer and Janneke S. Hoogstad-van Evert

Cancers 2025, 17(9), 1393; https://doi.org/10.3390/cancers17091393 - 22 Apr 2025

Abstract

Background: Cytoreductive surgery (CRS), in combination with chemotherapy, is the main treatment for advanced-stage ovarian cancer. In vulnerable patients, this extensive surgery has a high complication risk and may lead to clinical decline. There is emerging evidence that prehabilitation could be valuable [...] Read more.

Background: Cytoreductive surgery (CRS), in combination with chemotherapy, is the main treatment for advanced-stage ovarian cancer. In vulnerable patients, this extensive surgery has a high complication risk and may lead to clinical decline. There is emerging evidence that prehabilitation could be valuable in optimizing the patient’s condition prior to cytoreductive surgery, as is shown in colorectal surgery. However, there is limited evidence in gynecologic oncology. The objective of this study is to evaluate the feasibility and effects of implementing multimodal prehabilitation before cytoreductive surgery in patients with ovarian cancer. Methods: In two Dutch hospitals, 46 patients with ovarian cancer were included during the study period, of whom 32 participated in a multimodal prehabilitation program before CRS. The programs included at least physiotherapy, dietary advice and intoxication cessation. The timing, extent and content of the programs differed. Feasibility was assessed by eligibility and participation rates and adherence to the physiotherapy program. Effectiveness was measured by differences in functional capacity, postoperative outcomes and tolerance to adjuvant chemotherapy. Results: Eligibility rates in both hospitals were 83% and 89%, and participation rates were 68% and 72%. Adherence to the physiotherapy program was moderate and only satisfactory in 55% and 63% of the patients. All fitness endpoint measurements improved compared to the baseline. No significant differences in postoperative outcomes were found between prehabilitation and control patients. Prehabilitation patients appeared to have better tolerance to adjuvant chemotherapy, with fewer dose reductions (21% vs. 73%, p = 0.017) and dose deferrals (39% vs. 46%, not significant) compared to the control group. Conclusions: The implementation of multimodal prehabilitation before CRS is feasible and effective in patients with ovarian cancer with respectable eligibility and participation rates, along with improved functional capacity, even during neoadjuvant chemotherapy. Full article

(This article belongs to the Special Issue Gynecologic Oncology: Clinical and Translational Research)

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18 pages, 2800 KiB

Open AccessArticle

Microvascular Cortical Dynamics in Minimal Invasive Deep-Seated Brain Tumour Surgery

by José Pedro Lavrador, Oliver Wroe-Wright, Francesco Marchi, Ali Elhag, Andrew O’Keeffe, Pablo De La Fuente, Christos Soumpasis, Andrea Cardia, Ana Mirallave-Pescador, Alba Díaz-Baamonde Dias, Jose Sadio Mosquera, Domingos Coiteiro, Sharon Jewell, Anthony Strong, Richard Gullan, Keyoumars Ashkan, Francesco Vergani, Ahilan Kailaya Vasan and Ranjeev Bhangoo

Cancers 2025, 17(9), 1392; https://doi.org/10.3390/cancers17091392 - 22 Apr 2025

Abstract

Background: The tubular retractor-assisted minimally invasive parafascicular approach (trMIPS) is a transsulcal approach to deep-seated brain tumours. It is a safe surgical approach but its impact on the microvascular dynamics of the retracted cortex and its clinical implications are unknown. Methods: This was [...] Read more.

Background: The tubular retractor-assisted minimally invasive parafascicular approach (trMIPS) is a transsulcal approach to deep-seated brain tumours. It is a safe surgical approach but its impact on the microvascular dynamics of the retracted cortex and its clinical implications are unknown. Methods: This was a single-centre prospective study including patients with deep-seated brain tumours operated on with a trMIPS (BrainPath Nico System^©). All patients underwent pre- and post-cannulation indocyanine green study using a FLOW 800 module in a KINEVO Zeiss^© microscope. Speed, delay, time-to-peak (TtP) rise-in-time and cerebral blood flow index (CBFI) metrics were assessed. Results: Thirty-five patients were included, with 144 regions-of-interest (ROIs) selected. The majority of patients were diagnosed with glioblastoma (51.43%), and 37.14% of patients had a preoperative focal neurological deficit (FND) at presentation. A ROI-based analysis concluded that an increase in speed and CBFI was related with a worse neurological outcome when comparing the pre- and post-brain cannulation assessments (speed: deterioration = 43.12 ± 80.60% versus stable = −14.51 ± 57.80% versus improvement = 6.93 ± 31.33%, p < 0.0001; CBFI: deterioration = 50.40 ± 88.17% versus stable = −2.70 ± 67.54% versus improvement = −38.98 ± 26.17%, p = 0.0005). These findings were reproducible in a combined-ROI per patient analysis and confirmed after adjustment for confounding. Conclusion: Microvascular flow dynamics impact trMIPS outcomes as an increase in the speed and CBFI after decannulation was related with worse neurological outcome. Full article

(This article belongs to the Special Issue Emerging Research on Primary Brain Tumors)

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13 pages, 796 KiB

Open AccessArticle

The Prediagnostic General Practitioners’ Pathway of Gastrointestinal Stromal Tumor Patients: A Real-World Data Study

by Emily I. Holthuis, Verena Slijkhuis, Winette T. A. van der Graaf, Cas Drabbe, Winan J. van Houdt, Yvonne M. Schrage, Tim C. Olde Hartman, Annemarie Uijen, Neeltje Steeghs, Isabelle Bos, Marianne Heins and Olga Husson

Cancers 2025, 17(9), 1391; https://doi.org/10.3390/cancers17091391 - 22 Apr 2025

Abstract

Background/Objectives: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal (GI) tract, predominantly driven by KIT or PDGFRα oncogene mutations. Nonspecific symptoms contribute to diagnostic delays, with general practitioners (GPs) playing a pivotal role in early detection. However, studies on [...] Read more.

Background/Objectives: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal (GI) tract, predominantly driven by KIT or PDGFRα oncogene mutations. Nonspecific symptoms contribute to diagnostic delays, with general practitioners (GPs) playing a pivotal role in early detection. However, studies on GIST-specific primary care pathways are limited. This study examines GP contacts, diagnoses, and prescribed drugs in primary care during the 12 months preceding GIST diagnosis. Methods: This case-control study utilized data from the Netherlands Cancer Registry and Nivel Primary Care Database. It included 294 GIST patients diagnosed between 2010 and 2020 and 576 matched cancer-free controls. GP contacts, diagnoses, and newly prescribed drugs were analyzed across two time intervals: 0–4 and 5–12 months prediagnosis. Statistical comparisons were conducted using the Wilcoxon rank-sum test and descriptive analyses. Results: GIST cases had a median of six GP contacts (IQR 4–11) in the 12 months prediagnosis versus three (IQR 2–6) for controls (p < 0.05). Contacts increased 4 months before diagnosis, peaking 1 month prior. Common diagnoses in the 4-month interval included malignant neoplasms of the stomach (27.9%) and other digestive sites (27.6% and 11.2%), abdominal pain (9.5%), and iron deficiency anemia (9.5%). Newly prescribed drugs included proton pump inhibitors (13.9%) and osmotically acting laxatives (15.0%). Conclusions: This study highlights increased GP visits and specific reasons for these visits before GIST diagnosis. Future research should further examine GP records, not only through coded data but also unstructured data, and incorporate patient and GP perspectives to explore potential improvements in the diagnostic process. Full article

(This article belongs to the Special Issue The Evaluation of Cancer Treatment Patterns and Quality of Care across the World)

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12 pages, 1535 KiB

Open AccessArticle

Extreme Thrombocytosis in Patients with Overt Myelofibrosis and Its Clinical Associations

by Marko Lucijanic, Ivan Krecak, Ena Soric, Anica Sabljic, Davor Galusic, Hrvoje Holik, Vlatka Perisa, Martina Moric Peric, Ivan Zekanovic, Leonardo Budimir and Rajko Kusec

Cancers 2025, 17(9), 1390; https://doi.org/10.3390/cancers17091390 - 22 Apr 2025

Abstract

Background/Objectives: Overt primary myelofibrosis (PMF), secondary post-polycythemia vera (post-PV), and post-essential thrombocythemia (post-ET) myelofibrosis (SMF) are chronic myeloproliferative neoplasms (MPN) that sometimes present with extreme thrombocytosis (ExTh, platelet count > 1000 × 10⁹/L), a phenomenon of uncertain clinical significance since [...] Read more.

Background/Objectives: Overt primary myelofibrosis (PMF), secondary post-polycythemia vera (post-PV), and post-essential thrombocythemia (post-ET) myelofibrosis (SMF) are chronic myeloproliferative neoplasms (MPN) that sometimes present with extreme thrombocytosis (ExTh, platelet count > 1000 × 10⁹/L), a phenomenon of uncertain clinical significance since there are no published data available. Methods: We retrospectively investigated the clinical correlations and associated outcomes of ExTh in a cohort of 172 patients with overt myelofibrosis diagnosed in six Croatian hematology centers. Results: ExTh was present in 5.8% of patients and was associated with post-ET etiology of myelofibrosis, older age, smaller spleen size, and the presence of arterial hypertension (p < 0.05 for all analyses). No significant associations were observed with sex, degree of bone marrow fibrosis, or driver mutation status. Over the follow-up period, patients with ExTh experienced a favorable course regarding survival (p < 0.001) and bleeding risk (p = 0.034), whereas no significant association with thrombotic risk was observed (p = 0.682). Conclusions: In contrast to its context in ET, ExTh in overt fibrotic MPN does not appear to confer higher bleeding or thrombotic risk. Instead, it is associated with more favorable survival outcomes and reduced bleeding risk. Full article

(This article belongs to the Special Issue Novel Advances in the Molecular Understanding of Myeloproliferative Neoplasms (MPNs))

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17 pages, 3405 KiB

Open AccessArticle

Real-World Treatment Outcomes of Different Sequencing Options with Daratumumab, Lenalidomide, and Dexamethasone in Patients with Transplant-Ineligible Multiple Myeloma in Japan

by Kazuhito Suzuki, Yuma Fujimori, Chika Sakai, Hiroaki Tsuchiya and Yosuke Koroki

Cancers 2025, 17(9), 1389; https://doi.org/10.3390/cancers17091389 - 22 Apr 2025

Abstract

Multiple myeloma (MM) is a hematologic malignancy characterized by monoclonal proliferation of plasma cells that leads to bone disease, including lytic lesions and osteoporosis [...] Full article

(This article belongs to the Special Issue Multiple Myeloma: Recent Advances in Diagnosis, Analysis and Therapeutic Management)

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23 pages, 3202 KiB

Open AccessArticle

Lenalidomide Efficacy in Patients with MDS and Del-5q: Real-World Data from the Hellenic (Greek) National Myelodysplastic & Hypoplastic Syndromes Registry (EAKMYS)

by Argiris Symeonidis, Panagiotis Diamantopoulos, Athanasios Galanopoulos, Alexandra Kourakli, Eleni Sazakli, Eleftheria Hatzimichael, Maria Pagoni, Panagiotis Zikos, Theodoros P. Vassilakopoulos, Eleni Gavrilaki, Anthi Bouchla, Anna Kioumi, Katerina Palla, Ioannis Kotsianidis, Evridiki Michali, Zafiris Kartassis, Eirini Katodritou, Vasileios Lazaris, Maria Vagia, George Xanthopoulidis, Theodora Assimakopoulou, Charalampos Pontikoglou, Maria Dimou, Maria Dalekou-Tsolakou, Dimitra Liapi, Maria Kotsopoulou, Vassiliki Labropoulou, Menelaos Papoutselis, Despina Barmparousi, Efthymia Vlachaki, Georgia Kaiafa, Eleni Chandrinou, Panagiotis Karmas, Evangelos Terpos, George Vassilopoulos, Panayiotis Panayiotidis, Nora-Athina Viniou and Vassiliki Pappa Show full author list Hide full author list

Cancers 2025, 17(9), 1388; https://doi.org/10.3390/cancers17091388 - 22 Apr 2025

Abstract

Background-Objectives: Although considered standard of care for patients with low-/intermediate-1 risk MDS and isolated del(5q), lenalidomide is not widely used in patients exhibiting additional cytogenetic abnormalities, on top of del(5)q. The aim of this study was to provide real-world evidence for the efficacy [...] Read more.

Background-Objectives: Although considered standard of care for patients with low-/intermediate-1 risk MDS and isolated del(5q), lenalidomide is not widely used in patients exhibiting additional cytogenetic abnormalities, on top of del(5)q. The aim of this study was to provide real-world evidence for the efficacy of lenalidomide in patients with del(5q), with or without additional cytogenetic abnormalities. Methods: Patients with MDS exhibiting del(5q) in the Greek National Myelodysplastic Syndromes Registry were analyzed if they had received at least one lenalidomide dose and detailed response assessment/follow-up was available. Results: Among 238 patients analyzed, 153 (64.3%) had del(5q) syndrome (Group-I), 34 (14.3%) had an isolated del(5q) abnormality but were not 5q− syndrome (Group-II), 26 (10.9%) had del(5q) plus only one additional cytogenetic abnormality (Group-III), and 25 (10.5%) had del(5q) plus >1 additional abnormality (Group-IV). Among 218 (91.6%) evaluable patients, a major response was achieved by 146 (67.0%) patients, 114/146 (78.1%) in Group-I, 18/31 (58.1%) in Group-II, 10/20 (50.0%) in Group-III, and 4/21 (19.0%) in Group-IV. Overall, hematological response was seen in 177/218 (81.2%) patients, even among those with an excess of bone marrow blasts/frank acute myeloid leukemia. Duration of response was comparable between the four patient groups. A complete cytogenetic response was achieved by 38.0% overall, more commonly in Group-I (42.3%) and -III (35.7%). Transfusion-independent patients and those with a higher MCV or lower marrow blast cells at baseline had a higher probability of achieving a major response. With multivariate analysis, factors associated with overall survival were age, performance status, transfusion dependence, and marrow blast cell percentage at treatment start, as well as time from initial diagnosis to lenalidomide start. Conclusions: Lenalidomide was highly effective in patients with the del(5)q syndrome and also in those with isolated del(5)q, other than del(5)q syndrome, or those exhibiting del(5)q plus only one additional cytogenetic abnormality, not affecting chromosome 7. Full article

(This article belongs to the Special Issue Study on Acute Myeloid Leukemia)

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Cancers, Volume 17, Issue 9 (May-1 2025) – 35 articles

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