Cancers最新文献

{"title":"Mucin4 (MUC4) Antibody Labeled with an NIR Dye Brightly Targets Pancreatic Cancer Liver Metastases and Peritoneal Carcinomatosis.","authors":"Sunidhi Jaiswal, Siamak Amirfakhri, Javier Bravo, Keita Kobayashi, Abhijit Aithal, Sumbal Talib, Kavita Mallya, Maneesh Jain, Aaron M Mohs, Robert M Hoffman, Surinder K Batra, Michael Bouvet","doi":"10.3390/cancers17122031","DOIUrl":"10.3390/cancers17122031","url":null,"abstract":"<p><strong>Background/objectives: </strong>Pancreatic cancer is the fourth leading cause of deaths related to cancer. It is a highly aggressive malignancy and often metastasizes quickly to other parts of the body and organs. The most effective cure is surgical resection, which also is limited by tumor identification and clear tumor margin visualization. Previously, we used MUC4 antibodies labeled with IRDye800CW (anti-MUC4-IR800) to target primary human pancreatic cancer in orthotopic cell line mouse models.</p><p><strong>Methods: </strong>In the present study, we established a pancreatic cancer liver metastasis mouse model by implanting a tumor fragment in the liver and a peritoneal carcinomatosis mouse model by injecting pancreatic cancer cells interperitoneally. Once the tumors were established, anti-MUC4-IR800 was administered to the mice by tail vein injection. Laparotomy was performed and tumors were imaged under white-light and near-infrared (NIR) fluorescence with the Pearl Small Animal Imaging System.</p><p><strong>Results: </strong>NIR imaging after 72 h shows the bright targeting of pancreatic cancer metastasis in both mouse models with high tumor-to-background ratios.</p><p><strong>Conclusions: </strong>Anti-MUC4-IR800 was able to successfully target and brightly label metastatic pancreatic cancer as small as 1 mm. Future clinical applications of the results of the present study are discussed.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ISUP Grade Prediction of Prostate Nodules on T2WI Acquisitions Using Clinical Features, Textural Parameters and Machine Learning-Based Algorithms.","authors":"Teodora Telecan, Alexandra Chiorean, Roxana Sipos-Lascu, Cosmin Caraiani, Bianca Boca, Raluca Maria Hendea, Teodor Buliga, Iulia Andras, Nicolae Crisan, Monica Lupsor-Platon","doi":"10.3390/cancers17122035","DOIUrl":"10.3390/cancers17122035","url":null,"abstract":"<p><p><b>Background:</b> Prostate cancer (PCa) represents a matter at the forefront of healthcare, being divided into clinically significant (csPCa) and indolent PCa based on prognostic and treatment options. Although multi-parametric magnetic resonance imaging (mpMRI) has enabled significant advances, it cannot differentiate between the aforementioned categories; therefore, in order to render the initial diagnosis, invasive procedures such as transrectal prostate biopsy are still necessary. In response to these challenges, artificial intelligence (AI)-based algorithms combined with radiomics features offer the possibility of creating a textural pixel pattern-based surrogate, which has the potential of correlating the medical imagery with the pathological report in a one-to-one manner. <b>Objective</b>: The aim of the present study was to develop a machine learning model that can differentiate indolent from csPCa lesions, as well as individually classifying each nodule into corresponding ISUP grades prior to prostate biopsy, using textural features derived from mpMRI T2WI acquisitions. <b>Materials and Methods:</b> The study was conducted in 154 patients and 201 individual prostatic lesions. All cases were scanned using the same 1.5 Tesla mpMRI machine, employing a standard protocol. Each nodule was manually delineated using the 3D Slicer platform (version 5.2.2) and textural parameters were derived using the PyRadiomics database (version 3.1.0). We compared three machine learning classification models (Random Forest, Support Vector Machine, and Logistic Regression) in full, partial and no correlation settings, in order to differentiate between indolent and csPCa, as well as between ISUP 2 and ISUP 3 lesions. <b>Results</b>: The median age was 65 years (IQR: 61-69), the mean PSA value was 10.27 ng/mL, and 76.61% of the segmented lesions had a PI-RADS score of 4 or higher. Overall, the highest performance was registered for the Random Forest model in the partial correlation setting, differentiating between indolent and csPCa and between ISUP 2 versus ISUP 3 lesions, with accuracies of 88.13% and 82.5%, respectively. When the models were trained on combined clinical data and radiomic signatures, these accuracies increased to 91.11% and 91.39%, respectively. <b>Conclusions</b>: We developed a machine learning decision support tool that accurately predicts the ISUP grade prior to prostate biopsy, based on the textural features extracted from T2 MRI acquisitions.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTED: Kalicińska et al. Pneumonia in Patients with Chronic Lymphocytic Leukemia Treated with Venetoclax-Based Regimens: A Real-World Analysis of the Polish Adult Leukemia Group (PALG). <i>Cancers</i> 2024, <i>16</i>, 4168.","authors":"Elżbieta Kalicińska, Paula Jabłonowska-Babij, Marta Morawska, Elżbieta Iskierka-Jażdżewska, Joanna Drozd-Sokołowska, Ewa Paszkiewicz-Kozik, Łukasz Szukalski, Judyta Strzała, Urszula Gosik, Jakub Dębski, Iga Andrasiak, Anna Skotny, Krzysztof Jamroziak, Tomasz Wróbel","doi":"10.3390/cancers17122032","DOIUrl":"10.3390/cancers17122032","url":null,"abstract":"<p><p>The <i>Cancers</i> journal retracts the article titled \"Pneumonia in Patients with Chronic Lymphocytic Leukemia Treated with Venetoclax-Based Regimens: A Real-World Analysis of the Polish Adult Leukemia Group (PALG)\" [...].</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant Chemoradiotherapy or Radiotherapy Alone for Early Squamous Cervical Cancer with a Single Surgical-Pathological High-Risk Factor.","authors":"Ester P Olthof, Hans H B Wenzel, Jacobus van der Velden, Lukas J A Stalpers, Maaike A van der Aa, Constantijne H Mom","doi":"10.3390/cancers17122041","DOIUrl":"10.3390/cancers17122041","url":null,"abstract":"<p><p><b>Objective:</b> This study aims to explore the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone following a radical hysterectomy with pelvic lymphadenectomy. The study focuses on patients with clinically early-stage squamous cervical cancer who have a single high-risk factor postoperatively. <b>Methods:</b> This retrospective study included women diagnosed between 2001 and 2018, with: (1) clinical tumour (cT) stage 1A2-2A2, (2) cervical squamous carcinoma, (3) treated with radical hysterectomy and pelvic lymphadenectomy (4) followed by adjuvant (chemo)radiotherapy, and with (5) one high-risk factor (i.e., positive resection margins, parametrial involvement, or pelvic lymph node metastases). Recurrence-free and overall survival were estimated using Kaplan-Meier and Cox proportional hazards analyses. Inverse probability treatment weighting was used to adjust for confounding. <b>Results:</b> Of the 122 patients with squamous cell carcinoma and one high-risk factor, 76 (62%) received adjuvant chemoradiotherapy and 46 (38%) received adjuvant radiotherapy alone. Larger tumour size, tumour grade 3, and pathological parametrial invasion were more common in the radiotherapy group, while patients who received chemoradiotherapy were more likely to have multiple lymph node metastases. The unadjusted and for confounding adjusted 5-year survival rates were comparable between the adjuvant chemoradiotherapy and radiotherapy groups for both recurrence-free survival (85% versus 87%; <i>p</i> = 0.58, and 84% versus 91%; <i>p</i> = 0.49) and overall survival (84% versus 87%; <i>p</i> = 0.51, and 84% versus 91%; <i>p</i> = 0.49). <b>Conclusions:</b> Adding chemotherapy to radiotherapy may not improve survival of patients with early squamous cervical cancer treated with radical hysterectomy and pelvic lymphadenectomy, and with a single postoperative high-risk factor.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surgical Management of Oligometastatic Non-Small Cell Lung Cancer.","authors":"Susana Fortich, Deniz Piyadeoglu, Nafiye Busra Celik, Mara Antonoff","doi":"10.3390/cancers17122040","DOIUrl":"10.3390/cancers17122040","url":null,"abstract":"<p><p><b>Background:</b> Oligometastatic non-small cell lung cancer (NSCLC) represents a biologically and clinically distinct state characterized by limited metastatic spread. Increasing evidence suggests that aggressive local therapies, including surgical resection, may confer a survival benefit in this population. The objective of this review is to evaluate the current role of surgery in the management of oligometastatic NSCLC, with emphasis on patient selection, surgical strategy, integration with systemic therapy, and ongoing clinical investigations. <b>Methods:</b> This narrative review synthesizes retrospective and prospective clinical data, meta-analyses, major consensus guidelines, and ongoing trials since 2012. We highlight prognostic factors, staging strategies, and the evolving role of molecular and biomarker-based stratification. <b>Results:</b> Multiple retrospective studies and several randomized trials have demonstrated improved progression-free and overall survival with local consolidative therapy in oligometastatic NSCLC. Prognostic factors associated with favorable outcomes include a limited number of metastases (≤3), good performance status, absence of mediastinal nodal disease, metachronous presentation, and actionable molecular alterations. The integration of surgery with systemic therapies, including targeted agents and immunotherapy, has become increasingly common in selected patients. Ongoing trials such as LONESTAR, NORTHSTAR, and BRIGHTSTAR are expected to further define the role of surgery in this setting. <b>Conclusions:</b> Surgery is emerging as a key component of multimodal treatment for carefully selected patients with oligometastatic NSCLC. Future efforts should focus on refining patient selection through molecular stratification and expanding prospective trial data to guide personalized biology-driven treatment strategies.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive Factors Aiding in the Estimation of Intraoperative Resources in Gastric Cancer Oncologic Surgery.","authors":"Alexandru Blidișel, Mihai-Cătălin Roșu, Andreea-Adriana Neamțu, Bogdan Dan Totolici, Răzvan-Ovidiu Pop-Moldovan, Andrei Ardelean, Valentin-Cristian Iovin, Ionuț Flaviu Faur, Cristina Adriana Dehelean, Sorin Adalbert Dema, Carmen Neamțu","doi":"10.3390/cancers17122038","DOIUrl":"10.3390/cancers17122038","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Operating rooms represent valuable and pivotal units of any hospital. Therefore, their management affects healthcare service delivery through rescheduling, staff shortage/overtime, cost inefficiency, and patient dissatisfaction, among others. To optimize scheduling, we aim to assess preoperative evaluation criteria that influence the prediction of surgery duration for gastric cancer (GC) patients. In GC, radical surgery with curative intent is the ideal treatment. Nevertheless, the intervention sometimes must be palliative if the patient's status and tumor staging prove too advanced. <b>Methods:</b> A 6-year retrospective cohort study was performed in a tertiary care hospital, including all cases diagnosed with GC (ICD-10 code C16), confirmed through histopathology, and undergoing surgical treatment (N = 108). <b>Results:</b> The results of our study confirm male predominance (63.89%) among GC surgery candidates while bringing new perspectives on patient evaluation criteria and choice of surgical intervention (curative-Group 1, palliative-Group 2). Surgery duration, including anesthesiology (175.19 [95% CI (157.60-192.77)] min), shows a direct correlation with the number of lymph nodes dissected (<i>Surgical duration [min] = 10.67 × No. of lymph nodes removed - 32.25</i>). Interestingly, the aggressiveness of the tumor based on histological grade (highly differentiated being generally less aggressive than poorly differentiated) shows differential correlation with surgery duration among curative and palliative surgery candidates. Similarly, TNM staging indicates the need for a longer surgical duration (pTNM stage IIA, IIB, and IIIA) for curative interventions in patients with less advanced stages, as opposed to shorter surgery duration for palliative interventions (pTNM stage IIIC and IV). <b>Conclusions:</b> The study quantitatively presents the resources needed for the optimal surgical treatment of different groups of GC patients, as the disease coding systems in use regard the treatment of each pathology as \"standard\" in terms of patient management. The results obtained are anchored in the global perspectives of surgical outcomes and aim to improve the management of operating room scheduling, staff, and resources.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KAT/3BP: A Metabolism-Targeting Agent with Single and Combination Activity in Aggressive B-Cell Lymphomas.","authors":"Chiara Tarantelli, Filippo Spriano, Elisa Civanelli, Luca Aresu, Giorgia Risi, Eleonora Cannas, Omar Kayali, Luciano Cascione, Alberto J Arribas, Anastasios Stathis, Young H Ko, Francesco Bertoni","doi":"10.3390/cancers17122034","DOIUrl":"10.3390/cancers17122034","url":null,"abstract":"<p><strong>Background/objectives: </strong>Reprogramming of the cellular metabolism is a hallmark of cancer, offering therapeutic opportunities to target cancer cell vulnerabilities for therapeutic purposes. 3-Bromopyruvate (3BP) is a small alkylating agent that functions as an anti-metabolite, targeting key substrates in cancer metabolism and demonstrating antitumor activity across multiple cancer types. However, unformulated 3BP is associated with significant toxicity. This study investigates the efficacy of KAT/3BP, a clinical derivative of 3BP currently in phase 1 trials for hepatocellular carcinoma, in preclinical lymphoma models.</p><p><strong>Results: </strong><i>In vitro</i>, KAT/3BP exhibited cytotoxic activity across 12 lymphoma cell lines-including diffuse large B-cell lymphoma and mantle cell lymphoma-with a median IC₅₀ of 3.7 μM. It also remained effective against lymphoma cell lines with acquired resistance to FDA-approved therapies. <i>In vivo</i>, treatment with KAT/3BP led to reduced tumor size in a syngeneic mouse model, with the combination of oral and intratumoral administration showing the greatest efficacy. Furthermore, KAT/3BP demonstrated synergistic activity when combined with standard lymphoma therapies such as bendamustine and R-CHOP.</p><p><strong>Conclusions: </strong>Our findings highlight the potential of KAT/3BP as a novel therapeutic option, either as a single agent or in combination regimens, for treating lymphomas.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Time to Treatment Initiation on Quality of Response in Patients with Acute Myeloid Leukemia Receiving Intensive Chemotherapy.","authors":"Elisa Buzzatti, Giovangiacinto Paterno, Raffaele Palmieri, Fabiana Esposito, Lucia Cardillo, Kristian Taka, Lucrezia De Marchi, Marco Zomparelli, Kleda Zaganjori, Flavia Mallegni, Elisa Meddi, Federico Moretti, Ilaria Cerroni, Carmelo Gurnari, Luca Maurillo, Francesco Buccisano, Adriano Venditti, Maria Ilaria Del Principe","doi":"10.3390/cancers17122028","DOIUrl":"10.3390/cancers17122028","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) necessitates timely treatment, yet the impact of prolonged time to treatment (TTT) on clinical outcomes remains debated, especially its impact on achieving measurable residual disease (MRD) negativity, a powerful prognostic indicator in AML.</p><p><strong>Methods: </strong>This retrospective study analyzed 196 adult AML patients treated with intensive chemotherapy, evaluating the effect of TTT on outcome measures and quality of response. TTT was categorized arbitrarily into <8, 8-14, and >14 days.</p><p><strong>Results: </strong>Results showed a median TTT of 11 days. Median overall survival (OS) was 414 days, with no significant differences among TTT groups (<i>p</i> = 0.48). Complete remission rate was 75.5%, with significantly higher rates in patients treated within 14 days (<i>p</i> = 0.004 and <i>p</i> = 0.006 for 8-14 and <8 days, respectively) compared to >14 days. MRD was assessed in 140 patients, with 35% achieving negativity, and no significant differences observed among TTT groups.</p><p><strong>Conclusions: </strong>This study suggests that a treatment delay of up to 14 days does not negatively impact OS or MRD negativity. This timeframe potentially allows for thorough patient evaluation, including detailed genetic profiling and comorbidity assessment, facilitating a more personalized and optimized therapeutic strategy.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redefining the Use of Regorafenib and Trifluridine/Tipiracil Without Bevacizumab in Refractory Metastatic Colorectal Cancer: Findings from the ReTrITA Study.","authors":"Carlo Signorelli, Maria Alessandra Calegari, Annunziato Anghelone, Alessandro Passardi, Chiara Gallio, Alessandro Bittoni, Jessica Lucchetti, Lorenzo Angotti, Emanuela Di Giacomo, Ina Valeria Zurlo, Cristina Morelli, Emanuela Dell'Aquila, Adele Artemi, Donatello Gemma, Alessandra Emiliani, Marta Ribelli, Domenico Cristiano Corsi, Giulia Arrivi, Federica Mazzuca, Federica Zoratto, Mario Giovanni Chilelli, Marta Schirripa, Francesco Schietroma, Maria Grazia Morandi, Fiorenza Santamaria, Manuela Dettori, Antonella Cosimati, Rosa Saltarelli, Alessandro Minelli, Emanuela Lucci-Cordisco, Michele Basso","doi":"10.3390/cancers17122037","DOIUrl":"10.3390/cancers17122037","url":null,"abstract":"<p><p><i>Background:</i> Regorafenib (R) and trifluridine/tipiracil (T) are approved treatments for metastatic colorectal cancer (mCRC) in refractory cases. However, the optimal sequencing of these agents is unknown. The ReTrITA study planned to assess the real-world efficacy of R and T, administered either sequentially or as monotherapy, in a large Italian multicentre population. <i>Methods:</i> This retrospective observational analysis comprised 1156 mCRC patients treated between 2012 and 2023 at 17 Italian cancer centres. Patients were divided into four groups: sequential T/R (<i>n</i> = 261), sequential R/T (<i>n</i> = 155), R monotherapy (<i>n</i> = 313), and T monotherapy (<i>n</i> = 427). The primary objectives were overall survival (OS) and progression-free survival (PFS), with secondary goals being disease control rate, objective response rate, and treatment-related toxicity. <i>Results:</i> The monotherapy cohorts showed no significant difference in OS (R: 5.0 months; T: 5.9 months; <i>p</i> = 0.8371) or PFS (R: 3.2 months; T: 3.3 months; <i>p</i> = 0.6531). Compared to T/R, the sequential R/T group had significantly better outcomes: median OS was 16.6 vs. 12.6 months (HR = 0.67; <i>p</i> = 0.0004), and median PFS was 11.5 vs. 8.5 months (HR = 0.60; <i>p</i> < 0.0001). The survival advantage of R/T was consistent across clinical subgroups. The toxicity profiles were comparable with known safety data, with a lower prevalence of neutropenia reported in the R/T sequence. <i>Conclusions:</i> ReTrITA confirms the efficacy of R and T as monotherapies and provides compelling real-world evidence that the R/T sequence improves survival in refractory mCRC. These findings support a regorafenib-first approach in patients who are eligible, and they emphasise the need for future research into combination strategies and comparisons with newer drugs such as fruquintinib.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-Plasma Discharge Tube for Synergistic Glioblastoma Treatment.","authors":"William Murphy, Alex Horkowitz, Vikas Soni, Camil Walkiewicz-Yvon, Michael Keidar","doi":"10.3390/cancers17122036","DOIUrl":"10.3390/cancers17122036","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) resists current therapies due to its rapid proliferation, diffuse invasion, and heterogeneous cell populations. We previously showed that a single cold atmospheric plasma discharge tube (DT) reduces GBM viability via broad-spectrum electromagnetic (EM) emissions. Here, we tested whether two DTs arranged in a helmet configuration could generate overlapping EM fields to amplify the anti-tumor effects without thermal injury.</p><p><strong>Methods: </strong>The physical outputs of the single- and dual-DT setups were characterized by infrared thermography, broadband EM field probes, and oscilloscope analysis. Human U87-MG cells were exposed under the single or dual configurations. The viability was quantified with WST-8 assays mapped across 96-well plates; the intracellular reactive oxygen species (ROS), membrane integrity, apoptosis, and mitochondrial potential were assessed by multiparametric flow cytometry. Our additivity models compared the predicted versus observed dual-DT cytotoxicity.</p><p><strong>Results: </strong>The dual-DT operation produced constructive EM interference, elevating electric and magnetic field amplitudes over a broader area than either tube alone, while temperatures remained <39 °C. The single-DT exposure lowered the cell viability by ~40%; the dual-DT treatment reduced the viability by ~60%, exceeding the additive predictions. The regions of greatest cytotoxicity co-localized with the zones of highest EM field overlap. The dual-DT exposure doubled the intracellular ROS compared with single-DT and Annexin V positivity, confirming oxidative stress-driven cell death. The out-of-phase operation of the discharge tubes enabled the localized control of the treatment regions, which can guide future treatment planning.</p><p><strong>Conclusions: </strong>Two synchronously operated plasma discharge tubes synergistically enhanced GBM cell killing through non-thermal mechanisms that coupled intensified overlapping EM fields with elevated oxidative stress. This positions modular multi-DT arrays as a potential non-invasive adjunct or alternative to existing electric-field-based therapies for glioblastoma.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}