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14 pages, 545 KB  
Article
Anxiety and Depression in Breast Cancer Patients Before and After Chemotherapy: A Pre–Post Study Without a Control Group
by Magdalena Konieczny, Jolanta Sawicka, Izabela Gąska, Elżbieta Kaczmar, Małgorzata Pasek, Agnieszka Kiedik, Łukasz Rypicz and Dorota Kiedik
J. Clin. Med. 2025, 14(22), 8105; https://doi.org/10.3390/jcm14228105 - 16 Nov 2025
Cited by 1 | Viewed by 1022
Abstract
Background: Emotional disturbances such as anxiety and depression are common in breast cancer patients and may intensify during systemic therapy. This study aimed to assess changes in the severity of anxiety and depression among women undergoing neoadjuvant chemotherapy and to identify factors influencing [...] Read more.
Background: Emotional disturbances such as anxiety and depression are common in breast cancer patients and may intensify during systemic therapy. This study aimed to assess changes in the severity of anxiety and depression among women undergoing neoadjuvant chemotherapy and to identify factors influencing emotional outcomes. Methods: A total of 211 women with stage I–III breast cancer treated at the Podkarpackie Oncology Center in Brzozów, Poland, were included. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS) one week before and three weeks after chemotherapy. Statistical analyses were performed using the Wilcoxon signed-rank test and descriptive statistics (STATISTICA v.13). Results: After chemotherapy, anxiety and depression levels increased significantly. Nearly half of the patients experienced clinically relevant anxiety, and over one-third showed symptoms of depression. The emotional burden appeared particularly high among women reporting financial difficulties. In contrast, no clear associations were found with marital status, place of residence, or cancer stage. Conclusions: Chemotherapy in breast cancer patients is associated with a significant increase in anxiety and depression severity. Routine psychological assessment and psycho-oncological support should be implemented as integral components of oncological care, with particular attention to patients in disadvantaged socioeconomic conditions. Full article
(This article belongs to the Section Oncology)
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15 pages, 477 KB  
Article
The Impact of Different Hepatitis B Virus Serological Statuses on the Safety of Different Chemotherapy Regimens in Female Breast Cancer Patients: A Within-Subject Longitudinal Study
by Zhao-Xing Li, Dong-Li Liu, Lei Hu, Bai-Qing Peng, Xiu-Quan Qu, Li-Yuan Mu, Xiao-Chun Cheng, Pu Qiu, Yu-Xuan Huang, Xi-Rui Li and Ling-Quan Kong
Cancers 2025, 17(21), 3574; https://doi.org/10.3390/cancers17213574 - 5 Nov 2025
Cited by 1 | Viewed by 780
Abstract
Background: Breast cancer patients with hepatitis B virus (HBV) infection or past HBV infection face heightened risks of chemotherapy-induced hepatotoxicity and HBV reactivation (HBVr). This study aims to evaluate the impact of different HBV serological statuses on the safety of chemotherapy regimens based [...] Read more.
Background: Breast cancer patients with hepatitis B virus (HBV) infection or past HBV infection face heightened risks of chemotherapy-induced hepatotoxicity and HBV reactivation (HBVr). This study aims to evaluate the impact of different HBV serological statuses on the safety of chemotherapy regimens based on paclitaxel throughout the treatment cycle. Methods: This retrospective cohort study analyzed 4562 female breast cancer patients, categorized into three groups: 366 with HBV infection (HBsAg+), 2529 with past HBV infection (HBsAg−/HBcAb+), and 1667 without HBV infection (control group). The Primary events included liver injury, HBVr, treatment interruption, and laboratory indicator evaluation. Demographic characteristics and periodic laboratory parameters were recorded for within-subject longitudinal analysis. Results: Before chemotherapy, the incidence of liver injury was highest in the HBV-infected group (18.2%), intermediate in the past-infection group (13.2%), and lowest in the control group (12.0%). Throughout chemotherapy, the cumulative incidence of liver injury remained highest in the HBV-infected group (83.2%), compared to the past-infection (71.2%) and control (70.9%) groups. Chemotherapy interruption rates followed a similar gradient: 12.4% in the HBV-infected group, 6.9% in the past-infection group, and 5.5% in the control group. HBV-infected patients had a significantly higher risk of hepatotoxicity than controls during cycle 4 (relative risk 1.56, 95% CI 1.06 to 2.29) and cycle 5 (1.28, 1.09 to 1.75). HBVr occurred in 13 patients with HBV-infected. Conclusions: HBV serological status significantly impacts chemotherapy safety and treatment interruption. Prophylactic antiviral therapy and intensified monitoring during high-risk cycles (cycle 4 and cycle 5) are critical. These findings underscore the necessity of stratified management for HBV-affected breast cancer patients during chemotherapy. Full article
(This article belongs to the Special Issue New Perspectives in the Management of Breast Cancer)
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13 pages, 243 KB  
Review
The Evolving Role of Hematopoietic Stem Cell Transplantation in Philadelphia-like Acute Lymphoblastic Leukemia: From High-Risk Standard to Precision Strategies
by Matteo Molica, Claudia Simio, Laura De Fazio, Caterina Alati, Marco Rossi and Massimo Martino
Cancers 2025, 17(19), 3237; https://doi.org/10.3390/cancers17193237 - 5 Oct 2025
Viewed by 1255
Abstract
Background: Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype of B-cell ALL characterized by a gene expression profile similar to BCR::ABL1-positive leukemia, but lacking the BCR::ABL1 fusion gene. It is frequently associated with kinase-activating alterations, such as CRLF2 rearrangements, JAK-STAT pathway [...] Read more.
Background: Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype of B-cell ALL characterized by a gene expression profile similar to BCR::ABL1-positive leukemia, but lacking the BCR::ABL1 fusion gene. It is frequently associated with kinase-activating alterations, such as CRLF2 rearrangements, JAK-STAT pathway mutations, and ABL-class fusions. Patients with Ph-like ALL typically experience poor outcomes with conventional chemotherapy, underscoring the need for intensified and targeted therapeutic approaches. Methods: This review summarizes current evidence regarding the role of hematopoietic stem cell transplantation (HSCT) in patients with Ph-like ALL. We analyzed retrospective cohort studies, registry data, and ongoing clinical trials, focusing on transplant indications, molecular risk stratification, measurable residual disease (MRD) status, timing of transplant, and post-transplant strategies. Results: Retrospective data suggest that HSCT in first complete remission (CR1) may improve survival in patients with high-risk molecular lesions or MRD positivity at the end of induction. However, the lack of prospective data specific to Ph-like ALL limits definitive conclusions. Post-transplant relapse remains a challenge, and novel strategies, including the use of tyrosine kinase inhibitors or JAK inhibitors as post-HSCT maintenance therapy, are being explored. Emerging immunotherapies, such as chimeric antigen receptor (CAR) T cells, may reshape the therapeutic landscape and potentially alter the indications for transplantation. Conclusions: HSCT remains a crucial therapeutic option for selected patients with Ph-like ALL, particularly those with poor molecular risk features or persistent MRD. However, further prospective studies are needed to evaluate the indication for HSCT in CR1 and the potential integration of transplantation with targeted and immunotherapeutic strategies. Personalized treatment approaches based on genomic profiling and MRD assessment are essential to improve outcomes in this high-risk subset. Full article
(This article belongs to the Special Issue Hematopoietic Stem Cell Transplant in Hematological Malignancies)
16 pages, 1497 KB  
Article
Clinical and Molecular Characteristics of 100 Atypical Teratoid Rhabdoid Tumor Patients from Low- and Middle-Income Countries
by Noha A. Ismail, Shaimaa Aboubakr, Amal Mosaab, Eslam Maher, Hanafy Hafez, Hala Taha, Dina Yassin, Amal Refaat, Mohamed S. Zaghloul, Mohamed El-Beltagy, Abdelrahman Enayat, Volker Hovestadt, Olfat Ahmed, Mark W. Kieran, Ahmed El-Hemaly, Shahenda El-Naggar and Alaa El-Haddad
Cancers 2025, 17(18), 3077; https://doi.org/10.3390/cancers17183077 - 20 Sep 2025
Viewed by 1113
Abstract
Background: Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive, rare pediatric central nervous system malignancy. Prognostic factors for optimizing risk stratification and management in a large uniformly treated cohort are lacking. Methods: We conducted a single-center retrospective cohort study analyzing clinical and [...] Read more.
Background: Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive, rare pediatric central nervous system malignancy. Prognostic factors for optimizing risk stratification and management in a large uniformly treated cohort are lacking. Methods: We conducted a single-center retrospective cohort study analyzing clinical and outcome data for 100 newly diagnosed ATRT patients aged <18 years treated at the Children’s Cancer Hospital, Egypt, from 2008 to 2022. They were treated uniformly as per the Dana-Farber Cancer Institute modified IRS-III protocol. Molecular subgroups (MYC, SHH, and TYR) were determined via a DNA methylation array for patients who had sufficient DNA material available for the methylation analysis. Treatment toxicities were graded per the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: The median age at diagnosis was 1.88 years (IQR 0.99, 3.01); 28% were under 1 year of age, 45% were between 1 and 3 years old, and 26% were above 3 years of age. At diagnosis, 39% of patients had metastatic disease. A total of 60% of patients had gross residual disease following surgical excision. In multivariable analysis, age < 1 year and metastatic disease had a significant impact on event-free survival (EFS) (p = 0.047 and p = 0.002, respectively); however, only metastatic disease had a significantly negative effect on overall survival (OS) and cumulative incidence of relapse (CIR) (p = 0.002 for OS and p < 0.001 for CIR). DNA methylation was performed for 69 patients who were classified as having a TYR (n = 13), SHH (n = 34), MYC (n = 17), or non-ATRT diagnosis (n = 5). In the cohort of the 64 patients with ATRT defined by methylation, no significant survival differences were observed. Treatment-related deaths were reported in 28% of our studied group. Gram-negative septicemia was the most common cause of toxic death. The 5-year EFS and OS of the whole cohort were 12% and 13%, respectively. Conclusions: In this cohort, no significant survival differences were observed among the methylation subgroups. The higher treatment-related mortality in our cohort compared to the original protocol’s toxic-related deaths suggested that intensive and lengthy chemotherapy regimens may need modification for our population. The need for a short intensified approach, including a limited induction cycle followed by an intensified high-dose consolidation therapy, may be more appropriate for our patients with low socioeconomic status to avoid a repeated and prolonged course of protracted neutropenia. Full article
(This article belongs to the Special Issue Current Concept and Management of Pediatric ATRTs)
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13 pages, 449 KB  
Article
TCF Plus Radiochemotherapy Versus Neoadjuvant Radiochemotherapy Versus Flot Perioperative Chemotherapy in Esophageal Adenocarcinoma: The Results of a Three-Cohort, Multi-Centric Comparison: The A4 Study
by Marco Lorenzo Bonù, Giulia Volpi, Gloria Zanni, Jacopo Balduzzi, Fabrizia Terraneo, Giusto Pignata, Giuseppina Arcangeli, Francesco Frassine, Paola Vitali, Eliana La Rocca, Simone Giacopuzzi, Jacopo Weindelmayer, Carlo Alberto De Pasqual, Martina Milazzo, Michele Pavarana, Valentina Zen, Stefano De Pascale, Uberto Fumagalli Romario, Michela Buglione and Giovanni De Manzoni
Biomedicines 2025, 13(9), 2236; https://doi.org/10.3390/biomedicines13092236 - 11 Sep 2025
Viewed by 775
Abstract
Introduction: Recent randomized evidence suggests that stage II–IV non metastatic esophageal adenocarcinoma is best managed with perioperative chemotherapy (CHT) and surgery. Intensification of neoadjuvant chemotherapy and radiochemotherapy are proposed before surgery in high-volume centers with the aim of increasing both systemic and locoregional [...] Read more.
Introduction: Recent randomized evidence suggests that stage II–IV non metastatic esophageal adenocarcinoma is best managed with perioperative chemotherapy (CHT) and surgery. Intensification of neoadjuvant chemotherapy and radiochemotherapy are proposed before surgery in high-volume centers with the aim of increasing both systemic and locoregional control. However, few data comparing intensified RTCHT, CHT plus RTCHT and perioperative CHT with FLOT in real-life scenarios are available. Methods: This is a multicenter, retrospective series, including three cohorts of patients treated for esophageal adenocarcinoma: Cohort A: nRTCHT; Cohort B: TCF plus RTCHT, defined as triplet chemotherapy followed by dose-reduced triplet therapy + RT; Cohort C: perioperative chemotherapy with FLOT regimen. The primary endpoint was disease-free survival (DFS), and the secondary endpoints were pathologic complete response (pCR), pathologic lymph-node complete response (ypN0), overall survival (OS), and perioperative acute toxicity. Results: From January 2013 to December 2023, 142 patients were identified. All patients received multimodal therapy with radical esophagectomy. A total of 95% of patients were male; the majority of patients presented with stage cT3cN1. A total of 63 patients were treated in Cohort A (31 cases with doublet 5FU-CDDP concurrent to 50.4 Gy and 32 cases with CROSS regimen), 36 in Cohort B, and 43 in Cohort C. After a median FU of 36 months, the 3-year DFS resulted 58.6%. pCR occurred in 26 cases (18.6%). Three-year OS had a value of 72%. At univariate analysis, ypN0 was related to better DFS; cN+ disease was related with worse OS. The treatment cohort did not impact survival outcomes; however, an effect on CR was shown, with pCR in 15% (A), 36.3% (B), 11% (C) of cases, respectively (χ: 0.008). A total of 67% of patients in Cohort B experienced a ypN0. Two treatment-related deaths occurred (one in Cohort A and one in C) with a slight increase in G3 toxicity in cohort C. Conclusions: In this real-life multicenter series, oncological results were adequate for all three neoadjuvant strategies. TCF plus RTCHT guaranteed a higher pCR and ypN0 rate without increasing toxicity. An intensified neoadjuvant schedule, such as TCF plus RTCHT, may be useful in cases where higher tumor and nodal responses are needed. Taken together, our data highlight that further investigation is warranted before abandoning radiotherapy-based neoadjuvant approaches in esophageal and GEJ adenocarcinoma. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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14 pages, 1188 KB  
Review
Recent Advances in the Management of EGFR-Mutated Advanced Non-Small Cell Lung Cancer—A Narrative Review
by Prabhat Gautam Roy, Davida Reingold, Neha Pathak, Saurav Verma, Aarushi Gupta, Nicholas Meti, Consolacion Molto, Prabhat Singh Malik, Geordie Linford and Abhenil Mittal
Curr. Oncol. 2025, 32(8), 448; https://doi.org/10.3390/curroncol32080448 - 9 Aug 2025
Cited by 2 | Viewed by 4391
Abstract
The treatment landscape for EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) has evolved significantly with multiple combination regimens demonstrating superiority over single agent Osimertinib over the past two years. Recent trials such as FLAURA2 and MARIPOSA have explored intensified front-line regimens, with FLAURA2 [...] Read more.
The treatment landscape for EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) has evolved significantly with multiple combination regimens demonstrating superiority over single agent Osimertinib over the past two years. Recent trials such as FLAURA2 and MARIPOSA have explored intensified front-line regimens, with FLAURA2 demonstrating improvement in PFS with the addition of chemotherapy to Osimertinib and MARIPOSA, showing both a PFS and OS benefit with a novel combination regimen of Amivantamab and Lazertinib. However, these regimens are associated with significantly higher toxicity to patients and pose a huge financial and logistical burden to the health care system; therefore, treatment selection must therefore be individualized, considering disease biology, patient fitness, and toxicity burden. Post-progression strategies remain challenging due to resistance mechanisms like EGFR C797S mutations and MET amplification and the lack of data post-progression on novel first-line combinations. Ongoing trials are investigating fourth-generation EGFR TKIs, MET inhibitors, antibody–drug conjugates, and bispecific antibodies in subsequent lines. While regimens like Amivantamab-Lazertinib show promise even in second-line settings, toxicity, cost, and access remain barriers. As therapeutic options expand, biomarker-driven sequencing and personalized care will be critical to optimizing long-term outcomes in EGFR-mutated mNSCLC. Full article
(This article belongs to the Special Issue Hype or Hope—Combination Therapies for Lung Cancer)
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13 pages, 1488 KB  
Article
Validation of a Quantitative Ultrasound Texture Analysis Model for Early Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer: A Prospective Serial Imaging Study
by Daniel Moore-Palhares, Lakshmanan Sannachi, Adrian Wai Chan, Archya Dasgupta, Daniel DiCenzo, Sonal Gandhi, Rossanna Pezo, Andrea Eisen, Ellen Warner, Frances Wright, Nicole Look Hong, Ali Sadeghi-Naini, Mia Skarpathiotakis, Belinda Curpen, Carrie Betel, Michael C. Kolios, Maureen Trudeau and Gregory J. Czarnota
Cancers 2025, 17(15), 2594; https://doi.org/10.3390/cancers17152594 - 7 Aug 2025
Cited by 2 | Viewed by 1103
Abstract
Background/Objectives: Patients with breast cancer who do not achieve a complete response to neoadjuvant chemotherapy (NAC) may benefit from intensified adjuvant systemic therapy. However, such treatment escalation is typically delayed until after tumour resection, which occurs several months into the treatment course. Quantitative [...] Read more.
Background/Objectives: Patients with breast cancer who do not achieve a complete response to neoadjuvant chemotherapy (NAC) may benefit from intensified adjuvant systemic therapy. However, such treatment escalation is typically delayed until after tumour resection, which occurs several months into the treatment course. Quantitative ultrasound (QUS) can detect early microstructural changes in tumours and may enable timely identification of non-responders during NAC, allowing for earlier treatment intensification. In our previous prospective observational study, 100 breast cancer patients underwent QUS imaging before and four times during NAC. Machine learning algorithms based on QUS texture features acquired in the first week of treatment were developed and achieved 78% accuracy in predicting treatment response. In the current study, we aimed to validate these algorithms in an independent prospective cohort to assess reproducibility and confirm their clinical utility. Methods: We included breast cancer patients eligible for NAC per standard of care, with tumours larger than 1.5 cm. QUS imaging was acquired at baseline and during the first week of treatment. Tumour response was defined as a ≥30% reduction in target lesion size on the resection specimen compared to baseline imaging. Results: A total of 51 patients treated between 2018 and 2021 were included (median age 49 years; median tumour size 3.6 cm). Most were estrogen receptor–positive (65%) or HER2-positive (33%), and the majority received dose-dense AC-T (n = 34, 67%) or FEC-D (n = 15, 29%) chemotherapy, with or without trastuzumab. The support vector machine algorithm achieved an area under the curve of 0.71, with 86% accuracy, 91% specificity, 50% sensitivity, 93% negative predictive value, and 43% positive predictive value for predicting treatment response. Misclassifications were primarily associated with poorly defined tumours and difficulties in accurately identifying the region of interest. Conclusions: Our findings validate QUS-based machine learning models for early prediction of chemotherapy response and support their potential as non-invasive tools for treatment personalization and clinical trial development focused on early treatment intensification. Full article
(This article belongs to the Special Issue Clinical Applications of Ultrasound in Cancer Imaging and Treatment)
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27 pages, 395 KB  
Review
Nature-Inspired Strategies in Cancer Management: The Potential of Plant Extracts in Modulating Tumour Biology
by Marcin Hołota and Małgorzata M. Posmyk
Int. J. Mol. Sci. 2025, 26(14), 6894; https://doi.org/10.3390/ijms26146894 - 18 Jul 2025
Cited by 3 | Viewed by 2808
Abstract
Cancer is a serious group of diseases that is a huge problem on a global scale and is the second most common cause of death. Commonly used therapies do not always lead to the complete elimination of diseased cells or tissues and are [...] Read more.
Cancer is a serious group of diseases that is a huge problem on a global scale and is the second most common cause of death. Commonly used therapies do not always lead to the complete elimination of diseased cells or tissues and are also burdened with side effects that reduce the quality of life of patients. Due to these difficulties, new therapeutic approaches are still being sought. In recent years, there has been a return to interest in natural methods of treating various diseases, among which phytochemicals are particularly interesting. This article reviews plant extracts with anticancer properties with different mechanisms of action (proapoptotic, antiproliferative, antiangiogenic, immunomodulatory). In addition, plant extracts that reduce the side effects of chemotherapy and the limitations and prospects for the use of plant extracts in anticancer therapy are described. Our goal was to create an up-to-date information base that would encourage scientists to intensify research into supplementing targeted anticancer therapies with additional protective and preventive measures, in which natural mixtures of phytochemicals (plant extracts) are effective allies. At the same time, we encourage discussion on the limitations of their use in light of the orthodox principles of classical medicine and pharmacy (issues of safety, quality, drug purity, and dose precision), which are a priori correct but have not yet led to the elimination of cancer from the group of incurable diseases. Full article
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11 pages, 323 KB  
Article
Combined Hyperthermic Intraperitoneal Chemotherapy and Normothermic Intraperitoneal Chemotherapy Long-Term After Interval Cytoreduction in Ovarian Cancer: A Phase I Clinical Trial (BICOV1)
by Alida González-Gil, Elena Gil-Gómez, Vicente Olivares-Ripoll, Álvaro Cerezuela Fernández de Palencia, Jerónimo Martínez-García, Domingo Sánchez-Martínez, Alberto Rafael Guijarro-Campillo and Pedro Antonio Cascales-Campos
Cancers 2025, 17(12), 1957; https://doi.org/10.3390/cancers17121957 - 12 Jun 2025
Cited by 1 | Viewed by 2800
Abstract
Backgroud: Ovarian cancer is the deadliest gynecologic malignancy, with most patients presenting with peritoneal dissemination at diagnosis. Complete cytoreduction and sensitivity to platinum-based systemic chemotherapy remain the most significant prognostic factors. However, even after optimal first-line management, over half of patients relapse due [...] Read more.
Backgroud: Ovarian cancer is the deadliest gynecologic malignancy, with most patients presenting with peritoneal dissemination at diagnosis. Complete cytoreduction and sensitivity to platinum-based systemic chemotherapy remain the most significant prognostic factors. However, even after optimal first-line management, over half of patients relapse due to residual microscopic disease. Intraperitoneal chemotherapy aims to target this component, with normothermic intraperitoneal chemotherapy long-term (NIPEC-LT) and hyperthermic intraperitoneal chemotherapy (HIPEC) being the most studied approaches. While NIPEC-LT has demonstrated improved survival in select trials, concerns regarding toxicity and catheter-related complications have limited its adoption as standard care. Conversely, HIPEC has shown survival benefits, particularly in patients undergoing interval cytoreductive surgery (iCRS) after neoadjuvant chemotherapy, leading to its inclusion in clinical guidelines. However, HIPEC is administered as a single intraoperative treatment, limiting its prolonged effect. Objectives and Method: This study investigates the combination of HIPEC and postoperative NIPEC-LT in the BICOV-1 trial, a prospective, non-randomized phase I study evaluating the feasibility, safety, and oncologic outcomes. The primary objective is to assess the treatment completion rates and morbidity. The secondary endpoints include disease-free survival (DFS), overall survival (OS), and quality-of-life measures. Combining HIPEC and NIPEC-LT is a rational approach, as both have shown independent benefits and do not overlap in toxicity. HIPEC-induced biological changes may enhance the effectiveness of subsequent intraperitoneal chemotherapy. This trial will provide essential data for future phase II/III studies assessing the role of intensified intraperitoneal treatment in ovarian cancer management. Full article
(This article belongs to the Special Issue Research on Surgical Treatment for Ovarian Cancer)
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21 pages, 5367 KB  
Case Report
History of an Insidious Case of Metastatic Insulinoma
by Katarzyna Antosz-Popiołek, Joanna Koga-Batko, Wojciech Suchecki, Małgorzata Stopa, Katarzyna Zawadzka, Łukasz Hajac, Marek Bolanowski and Aleksandra Jawiarczyk-Przybyłowska
J. Clin. Med. 2025, 14(12), 4028; https://doi.org/10.3390/jcm14124028 - 6 Jun 2025
Viewed by 1384
Abstract
In this article, we present a case of a 49-year-old woman presenting with a recurrent metastatic neuroendocrine tumor. Background: Insulinomas are neuroendocrine tumors derived from beta cells of the pancreas that secrete insulin. Usually, they are benign tumors; however, metastatic insulinomas are [...] Read more.
In this article, we present a case of a 49-year-old woman presenting with a recurrent metastatic neuroendocrine tumor. Background: Insulinomas are neuroendocrine tumors derived from beta cells of the pancreas that secrete insulin. Usually, they are benign tumors; however, metastatic insulinomas are an extremely rare malignant form of these tumors, carrying a significantly worse prognosis. Case Presentation: A 49-year-old woman, a patient in the University Hospital in Wroclaw in the Department of Endocrinology, Diabetes and Isotope Therapy, first presented with abdominal pain in 2009, when ultrasound and further examination led to the diagnosis of a tumor in the pancreas (a solid pseudopapillary tumor of the pancreas—meta NET G2), and the patient underwent distal pancreatectomy with splenectomy. For ten years, she was under observation, and her symptoms, such as abdominal pain, nausea, weight loss, and general weakness, reappeared in 2019. Then, magnetic resonance imaging (MRI) showed a lesion in the liver, and further histopathology revealed neuroendocrine tumor (NET) metastasis to the liver. In 2022, the patient presented with loss of consciousness and convulsion, loss of weight, and hypoglycemia after meals. In April 2022, the daily glycemic profile was recorded and a 72 h fasting test was performed; however, their results excluded insulinoma. Positron emission tomography–computed tomography (PET-CT) with 18F-fluorodeoxyglucose (18F-FDG) and PET with gallium-68-DOTA-(Tyr3)-octreotate (68Ga-DOTA-TATE) showed a metastatic proliferative process in the liver. Persistent hypoglycemia led to another hospitalization in May 2022, and repeated tests allowed for the diagnosis of insulinoma. Treatment with somatostatin analogs and diazoxide was started. A CT scan in November 2022 and a PET scan in January 2023 showed new metastases to the liver, bones, and cervical lymph nodes, and it was decided to intensify the treatment. In May 2023, the patient was qualified for Lutathera treatment for insulinoma at the University Clinical Hospital in Poznań. In June 2023, another disturbing symptom was reported by the patient, a painful lump in the breast. During diagnostics, metastases with high proliferation markers were found in both breasts. Two months later, in August 2023, the patient received another dose of Lutathera. In October 2023, significant progression of liver lesions, metastases to bones of the spine, ribs, and pelvis, and periaortic and pelvic lymphadenopathy were found as well as elevated values of neuron-specific enolase and calcitonin. The patient was also referred to the Palliative Medicine Home Hospice. In consultation with the Lower Silesian Cancer Center, the decision was made to forgo further treatment with PRRT and initiate systemic chemotherapy. Despite the chosen treatment, the patient died on 27/DEC/2023. Conclusions: This case report can serve clinicians, as it presents a case of an extremely rare and insidious tumor, metastatic insulinoma. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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18 pages, 7757 KB  
Article
Modeling the Transitional Phase of Epithelial Cells Reveals Prognostic and Therapeutic Targets in Pancreatic Ductal Adenocarcinoma
by Linhan Ye, Zongyao Chen, Jingcheng Zhang and Qiaolin Li
Cancers 2025, 17(11), 1813; https://doi.org/10.3390/cancers17111813 - 29 May 2025
Viewed by 1109
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis, and its progression is driven by epithelial plasticity and tumor microenvironment remodeling. Finding biomarkers that are responsible for the turning point from the early stage to the aggressive phase would [...] Read more.
Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis, and its progression is driven by epithelial plasticity and tumor microenvironment remodeling. Finding biomarkers that are responsible for the turning point from the early stage to the aggressive phase would facilitate clinical management. Method: In this study, we employed single-cell RNA sequencing to characterize a distinct subpopulation of highly proliferative epithelial cells undergoing a transitional phase during PDAC progression. By linking to cell cycle dysregulation, epithelial differentiation, and clinical staging, we constructed a gene-based risk score model using Lasso Cox regression. The expression of selected genes within the model was further validated using qPCR. Results: The model demonstrated robust predictive power for patient prognosis, TNM staging, and chemotherapy sensitivity. Further analysis of the tumor microenvironment revealed intensified crosstalk between a specific fibroblast subpopulation and transitional epithelial cells, mediated largely by collagen signaling. This stromal–epithelial interaction was found to contribute to the fibrotic barrier characteristic of PDAC. Additionally, immune profiling uncovered altered infiltration patterns, particularly involving natural killer (NK) cells in high-risk patients, suggesting mechanisms of immune tolerance and inhibition. Conclusions: These findings offer potential avenues for early detection, risk stratification, and targeted therapeutic strategies in PDAC. Full article
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16 pages, 624 KB  
Review
Advances in Current Treatment Paradigms for Metastatic Hormone-Sensitive Prostate Cancer
by Shayan Smani, Julien DuBois, Ismail Ajjawi, Nishan Sohoni, Ankur U. Choksi, Soum D. Lokeshwar, Isaac Y. Kim and Joseph F. Renzulli
J. Clin. Med. 2025, 14(8), 2565; https://doi.org/10.3390/jcm14082565 - 8 Apr 2025
Cited by 1 | Viewed by 8866
Abstract
Metastatic hormone-sensitive prostate cancer (mHSPCa) presents de novo or represents significant disease progression and requires systemic treatment. However, progression to castration resistance is inevitable. The treatment landscape has evolved with the introduction of intensified systemic therapy, including androgen deprivation therapy (ADT) combined with [...] Read more.
Metastatic hormone-sensitive prostate cancer (mHSPCa) presents de novo or represents significant disease progression and requires systemic treatment. However, progression to castration resistance is inevitable. The treatment landscape has evolved with the introduction of intensified systemic therapy, including androgen deprivation therapy (ADT) combined with either androgen receptor signaling inhibitors (ARSIs) or cytotoxic chemotherapy (doublet therapy) or combined therapy with both agents (triplet therapy). Landmark trials such as CHAARTED, STAMPEDE, LATITUDE, ENZAMET, and TITAN have established combination therapies as the standard of care, demonstrating significant overall survival benefits. More recently, triplet therapy—integrating ADT, docetaxel, and an ARSI—has emerged as an effective approach, particularly in high-volume metastatic disease, as supported by ARASENS and PEACE-1. Advances in imaging, such as PSMA PET-CT, have improved disease detection, allowing earlier detection of metastasis and appropriate therapy. Similarly, genomic profiling has enabled biomarker-driven, personalized treatment strategies. The role of treatment of the primary tumor, by either radiation therapy or cytoreductive prostatectomy, in low-volume disease continues to be explored. As novel therapies, targeted agents, and immunotherapies undergo investigation, optimizing treatment selection based on disease burden, molecular characteristics, and patient factors will be essential. The future of mHSPCa management lies in multidisciplinary, precision-based approaches to improve patient outcomes while balancing treatment efficacy and tolerability. Full article
(This article belongs to the Special Issue Evolving Therapies in Metastatic Prostate Cancer)
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21 pages, 2634 KB  
Systematic Review
Natural Products for Melanoma Therapy: From Traditional Medicine to Modern Drug Discovery
by Soojin An, Jeongeun An, Dain Lee, Han Na Kang, Sojin Kang, Chi-Hoon Ahn, Rony Abdi Syahputra, Rosy Iara Maciel A. Ribeiro and Bonglee Kim
Plants 2025, 14(6), 951; https://doi.org/10.3390/plants14060951 - 18 Mar 2025
Cited by 4 | Viewed by 5594
Abstract
Melanoma, a type of skin cancer originating from melanocytes, represents a significant public health concern according to the World Health Organization. It is one of the most commonly diagnosed cancers worldwide, particularly affecting populations in Europe and North America, with an increasing incidence [...] Read more.
Melanoma, a type of skin cancer originating from melanocytes, represents a significant public health concern according to the World Health Organization. It is one of the most commonly diagnosed cancers worldwide, particularly affecting populations in Europe and North America, with an increasing incidence in Asia. The rise emphasizes the need for diversified treatment approaches. Conventional treatments for melanoma, including immunotherapy, chemotherapy, and targeted therapies like the FDA-approved Opdivo and Relatlimab, often come with severe side effects and high relapse rates. Consequently, natural products have gained considerable attention for their potential to enhance therapeutic outcomes and reduce adverse effects. This systematic review evaluates the anti-cancer properties of natural products against melanoma, examining 52 studies from PubMed and Google Scholar. Our analysis focuses on the antioxidant, anti-angiogenesis, anti-metastatic, and apoptosis-inducing activities of these compounds, also discussing the regulatory factors involved. The findings advocate for intensified research into natural products as complementary agents in melanoma treatment, aiming to improve efficacy and patient quality of life. Further in vitro, in vivo, and clinical trials are essential to validate their effectiveness and integrate them into standard care protocols. Full article
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16 pages, 2514 KB  
Review
Circulating Tumor DNA as a Real-Time Biomarker for Minimal Residual Disease and Recurrence Prediction in Stage II Colorectal Cancer: A Systematic Review and Meta-Analysis
by Silvia Negro, Alessandra Pulvirenti, Chiara Trento, Stefano Indraccolo, Stefania Ferrari, Marco Scarpa, Emanuele Damiano Luca Urso, Francesca Bergamo, Salvatore Pucciarelli, Simona Deidda, Angelo Restivo, Sara Lonardi and Gaya Spolverato
Int. J. Mol. Sci. 2025, 26(6), 2486; https://doi.org/10.3390/ijms26062486 - 11 Mar 2025
Cited by 12 | Viewed by 6497
Abstract
The role of adjuvant chemotherapy (adj-CT) in stage II colon cancer remains controversial. Circulating tumor DNA (ctDNA) is a promising biomarker for detecting minimal residual disease (MRD) and predicting recurrence. This systematic review and meta-analysis evaluated the prognostic value of ctDNA in stage [...] Read more.
The role of adjuvant chemotherapy (adj-CT) in stage II colon cancer remains controversial. Circulating tumor DNA (ctDNA) is a promising biomarker for detecting minimal residual disease (MRD) and predicting recurrence. This systematic review and meta-analysis evaluated the prognostic value of ctDNA in stage II colorectal cancer (CRC), focusing on postoperative detection, post adj-CT outcomes, and dynamic surveillance. A literature search identified studies correlating ctDNA positivity in stage II CRC with recurrence risk, recurrence-free survival (RFS), and disease-free survival (DFS). Seven studies met the inclusion criteria. Postoperative ctDNA positivity significantly increased the risk of recurrence (pooled risk ratio [RR:] 3.66; 95% confidence interval [CI]: 1.25–10.72; p = 0.002). CtDNA positivity after adj-CT was strongly associated with poor survival, while dynamic ctDNA monitoring detected recurrence earlier than conventional methods, including carcinoembryonic antigen (CEA) and imaging. CtDNA is a robust prognostic biomarker in stage II CRC, enabling personalized treatment. High-risk ctDNA-positive patients may benefit from intensified therapy, while ctDNA-negative patients could avoid unnecessary treatments. However, the standardization of detection methods and large-scale validation studies are needed before integrating ctDNA into routine clinical practice as a non-invasive, dynamic tool for personalized care. Full article
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20 pages, 1511 KB  
Article
Dose Escalation in Neoadjuvant Chemoradiotherapy for Rectal Cancer: Short-Term Efficacy and Toxicity of VMAT–SIB vs. 3D-CRT
by Suzana Stojanovic-Rundic, Mladen Marinkovic, Aleksandra Stanojevic, Dusica Gavrilovic, Radmila Jankovic, Natasa Maksimovic, Aleksandar Tomasevic, Predrag Petrasinovic, Sandra Radenkovic and Milena Cavic
Medicina 2025, 61(3), 483; https://doi.org/10.3390/medicina61030483 - 11 Mar 2025
Cited by 3 | Viewed by 2549
Abstract
Background and Objectives: The standard treatment for locally advanced rectal cancer (LARC) includes neoadjuvant chemoradiotherapy (nCRT), followed by surgery with or without adjuvant chemotherapy (CT). This study evaluated the efficacy and safety of dose-escalated radiotherapy (RT) using the volumetric modulated arc therapy–simultaneous [...] Read more.
Background and Objectives: The standard treatment for locally advanced rectal cancer (LARC) includes neoadjuvant chemoradiotherapy (nCRT), followed by surgery with or without adjuvant chemotherapy (CT). This study evaluated the efficacy and safety of dose-escalated radiotherapy (RT) using the volumetric modulated arc therapy–simultaneous integrated boost (VMAT–SIB) technique in patients with LARC compared to 3D conformal radiotherapy (3D-CRT). Materials and Methods: This study prospectively enrolled 75 patients with LARC. All patients received nCRT using VMAT–SIB, delivering a tumor dose (TD) of 54 Gy in 25 fractions, with concomitant CT following the 5-fluorouracil and leucovorin (5-FU–LV) protocol. To compare the treatment outcomes and toxicity associated with the increased RT dose, a retrospective cohort of 62 patients treated with the 3D-CRT technique was analyzed. The 3D-CRT group received a TD of 50.4 Gy in 28 fractions with the same CT. Outcomes, including pathological complete response (pCR), tumor regression grade (TRG), and sphincter preservation rates, were compared. Results: Among operated patients, the group treated with VMAT–SIB demonstrated improved rates of pCR (20.6% vs. 8.9%), with a statistically significant trend (p = 0.06). Sphincter-preserving surgeries were performed in 49 out of 63 operated patients (77.8%) in the VMAT–SIB group, compared to 35 out of 56 (62.5%) in the 3D-CRT group. Analysis of the definitive postoperative stage revealed a significantly higher prevalence of lower T categories (T0–2) (p < 0.01), negative N status (p < 0.05), and lower stages (I + II) (p < 0.05) in patients treated with the intensified RT approach. However, no significant differences in acute toxicity were observed. Conclusions: The implementation of intensified treatment with a higher dose using the VMAT–SIB technique demonstrated significant benefits in downsizing and downstaging compared to the standard treatment approach. These findings support its integration into clinical practice. However, further prospective, multi-center studies are needed to validate these results and assess long-term outcomes. Full article
(This article belongs to the Section Oncology)
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