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Evolution of Potentially Actionable Genomic Alterations in Advanced Prostate Cancer: A Real-World Analysis of Serial Circulating Tumor DNA Testing. 晚期前列腺癌中潜在可操作的基因组改变的进化:一系列循环肿瘤DNA测试的真实世界分析。
IF 4.4 2区 医学
Cancers Pub Date : 2025-09-18 DOI: 10.3390/cancers17183048
Miguel Muniz, L Jill Tsai, Jacob J Orme, Leslie A Bucheit, Spyridon P Basourakos, Nancy Wei, Regina M Koch, Zachary Scharf, Sounak Gupta, Adam M Kase, Rodrigo Rodrigues Pessoa, Irbaz B Riaz, Eugene D Kwon, Jack R Andrews, Daniel S Childs
{"title":"Evolution of Potentially Actionable Genomic Alterations in Advanced Prostate Cancer: A Real-World Analysis of Serial Circulating Tumor DNA Testing.","authors":"Miguel Muniz, L Jill Tsai, Jacob J Orme, Leslie A Bucheit, Spyridon P Basourakos, Nancy Wei, Regina M Koch, Zachary Scharf, Sounak Gupta, Adam M Kase, Rodrigo Rodrigues Pessoa, Irbaz B Riaz, Eugene D Kwon, Jack R Andrews, Daniel S Childs","doi":"10.3390/cancers17183048","DOIUrl":"10.3390/cancers17183048","url":null,"abstract":"<p><p><b>Background:</b> Longitudinal genomic profiling through serial circulating tumor DNA (ctDNA) testing offers a noninvasive method to monitor clonal evolution in advanced prostate cancer. This study evaluated the frequency and nature of newly emergent and potentially actionable genomic alterations detected through serial testing in a real-world setting. <b>Methods:</b> We conducted a retrospective analysis of advanced prostate cancer patients who underwent multiple Guardant360 ctDNA tests between October 2020 and March 2023. The study focused on identifying new genomic alterations absent in the initial test, with particular attention to alterations relevant for on-label therapies, therapies approved in other oncologic indications (i.e., off-label), or a clinical trial. <b>Results:</b> Among 479 patients with at least two ctDNA tests, the median interval between the first and second evaluable tests was 207 days. New and potentially actionable alterations emerged in 57.8% of patients, including potential targets for on-label therapies (16.7%), off-label therapies (16.5%), and clinical trials (55.7%). Tumor mutational burden (TMB) increased from \"low\" to \"high\" in 11% of patients, although none had microsatellite instability or mismatch repair deficiency. In a Mayo Clinic subset, ten patients received olaparib based on treatment-emergent alterations, but none achieved a prostate-specific antigen (PSA) response. Two patients who transitioned from low to high TMB received pembrolizumab, both with progressive disease as best response. <b>Conclusions:</b> In a large real-world cohort, serial ctDNA testing frequently identified new alterations that were not detected at baseline and are potentially actionable therapeutic targets, highlighting the value of serial genomic profiling for capturing clonal dynamics. Additional research is needed to better establish a framework for retesting and to clarify how these results should influence subsequent treatment decisions.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173952","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}
引用次数: 0
Prevalence and Clinical Significance of Potential Drug-Drug Interactions in Hospitalized Pediatric Oncology Patients: A Prospective Pharmacoepidemiologic Study. 住院儿科肿瘤患者潜在药物-药物相互作用的患病率及临床意义:一项前瞻性药物流行病学研究。
IF 4.4 2区 医学
Cancers Pub Date : 2025-09-18 DOI: 10.3390/cancers17183054
Omid Reza Zekavat, Narjes Zarsanj, Adel Sadeghdoust, Alekhya Lavu, Mohammadreza Bordbar, Sherif Eltonsy, Payam Peymani
{"title":"Prevalence and Clinical Significance of Potential Drug-Drug Interactions in Hospitalized Pediatric Oncology Patients: A Prospective Pharmacoepidemiologic Study.","authors":"Omid Reza Zekavat, Narjes Zarsanj, Adel Sadeghdoust, Alekhya Lavu, Mohammadreza Bordbar, Sherif Eltonsy, Payam Peymani","doi":"10.3390/cancers17183054","DOIUrl":"10.3390/cancers17183054","url":null,"abstract":"<p><strong>Background: </strong>Drug-drug interactions (DDIs) are frequent and potentially harmful in pediatric cancer patients due to polypharmacy and complex chemotherapy regimens. However, data on DDIs in hospitalized pediatric oncology patients remain limited, particularly in Middle Eastern settings.</p><p><strong>Methods: </strong>In this prospective study, we analyzed prescriptions for hospitalized pediatric oncology patients in Iran to assess the prevalence, severity, and nature of potential DDIs (PDDIs). Chemotherapy and supportive medications were analyzed using two validated databases (Lexi-Interact™ and Drugs.com™) between November 2019 and June 2020.</p><p><strong>Results: </strong>Of 80 patients (median age 8.9 years), 21.2% had at least one documented PDDI. We identified 197 total PDDIs involving 42 unique drug pairs. The most common DDIs included acetaminophen and granisetron (severity rating: moderate). Methotrexate and vincristine were the most frequent antineoplastic DDI pair. Methotrexate alone accounted for 156 interactions.</p><p><strong>Conclusions: </strong>This is the first prospective study from Iran-and the largest in the region-investigating PDDIs in pediatric oncology. The dual-database screening approach improved PDDI detection. Clinical teams should routinely evaluate medication profiles in pediatric cancer patients to minimize avoidable harms from DDIs.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12469098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173489","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}
引用次数: 0
Lipid Storage and Therapy Resistance in Chronic Myeloid Leukaemia: A Novel Perspective on Targeting Metabolic Vulnerabilities. 慢性髓性白血病的脂质储存和治疗抵抗:针对代谢脆弱性的新视角。
IF 4.4 2区 医学
Cancers Pub Date : 2025-09-17 DOI: 10.3390/cancers17183033
Molly Tolland, David M Ross, Deborah White, Timothy P Hughes, Ilaria S Pagani
{"title":"Lipid Storage and Therapy Resistance in Chronic Myeloid Leukaemia: A Novel Perspective on Targeting Metabolic Vulnerabilities.","authors":"Molly Tolland, David M Ross, Deborah White, Timothy P Hughes, Ilaria S Pagani","doi":"10.3390/cancers17183033","DOIUrl":"10.3390/cancers17183033","url":null,"abstract":"<p><p>While there have been outstanding improvements in the treatment of Chronic Myeloid Leukaemia (CML), some patients do not respond optimally or are entirely resistant to treatment. In many of these patients, the molecular basis for resistance to tyrosine kinase inhibitors (TKIs) is unknown, highlighting the need for further investigation. Various potential mechanisms of TKI resistance are being explored with the aim of identifying new therapeutic options. A growing body of evidence suggests that alterations in lipid metabolism are implicated in treatment resistance in a variety of cancers including CML. Intracellular lipid storage may play a protective role to facilitate drug resistance in cancers and subsequently could serve as a targetable vulnerability. Due to the single genetic driver of oncogenesis, CML is an excellent model disease for studying metabolic alterations in cancer that contribute to drug resistance and disease progression. Based on the need to identify adjuvant therapies for TKI-resistant CML, we have evaluated evidence of dysregulated lipid storage in CML and its potential as a therapeutic target. In addition to in vitro analysis, we discuss the outcomes of clinical studies of CML treated with therapeutics that target lipid storage both directly and indirectly. We also highlight key limitations in the current literature and identify priority areas for further investigation. Advancing our understanding of lipid metabolic pathways, including lipid storage, in CML may reveal actionable vulnerabilities and support the development of novel therapeutic strategies to overcome TKI resistance.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173802","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}
引用次数: 0
Carbon-Ion Radiotherapy for Prostate Cancer in Patients with a History of Surgery for Benign Prostatic Hyperplasia. 有良性前列腺增生手术史的前列腺癌患者的碳离子放疗。
IF 4.4 2区 医学
Cancers Pub Date : 2025-09-17 DOI: 10.3390/cancers17183039
Atsushi Okato, Kosei Miura, Tomoki Yamaguchi, Mio Nakajima, Hirokazu Makishima, Takanobu Utsumi, Koichiro Akakura, Hiroyoshi Suzuki, Masaru Wakatsuki, Hiroshi Tsuji, Tomohiko Ichikawa, Hitoshi Ishikawa
{"title":"Carbon-Ion Radiotherapy for Prostate Cancer in Patients with a History of Surgery for Benign Prostatic Hyperplasia.","authors":"Atsushi Okato, Kosei Miura, Tomoki Yamaguchi, Mio Nakajima, Hirokazu Makishima, Takanobu Utsumi, Koichiro Akakura, Hiroyoshi Suzuki, Masaru Wakatsuki, Hiroshi Tsuji, Tomohiko Ichikawa, Hitoshi Ishikawa","doi":"10.3390/cancers17183039","DOIUrl":"10.3390/cancers17183039","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Carbon-ion radiotherapy (CIRT) offers precise dose distribution and enhanced biological effectiveness in localized prostate cancer. However, the safety of CIRT in patients with a history of surgery for benign prostatic hyperplasia (BPH), such as transurethral resection of the prostate (TURP), remains unclear. This study aimed to evaluate the long-term safety and oncological outcomes of CIRT in this population. <b>Methods:</b> A retrospective analysis was conducted in 74 of 3848 patients with prostate cancer and a history of surgery for BPH who underwent CIRT combined with risk-adapted androgen deprivation therapy between 2007 and 2023. Adverse events were assessed using CTCAE v5.0. Biochemical recurrence-free survival was estimated using the Kaplan-Meier method and risk factors for hematuria with multivariate logistic regression and receiver operation characteristic (ROC) analysis. <b>Results:</b> CIRT was generally well-tolerated. Early Grade 2 genitourinary (GU) adverse events occurred in 5.4% of patients, and late-Grade 2 or higher GU events occurred in 8.1%. The cumulative incidence of Grade 2 ≥ GU events remained 10% at 36 months. Compared to holmium laser enucleation of the prostate, a shorter interval between BPH surgery and CIRT initiation and a history of TURP were independently associated with an increased risk of hematuria. Notably, 5-year bRFS was 100% in low- and intermediate-risk groups and 88.6% in the high-risk group. <b>Conclusions:</b> CIRT demonstrates acceptable oncological outcomes and urinary complication rates in patients with prostate cancer and a history of BPH surgery. These findings suggest that CIRT can be a feasible treatment option in this surgically altered population, but careful patient selection, individualized treatment planning, and long-term follow-up are essential. Given the absence of a non-BPH control group, oncological efficacy should be interpreted with caution.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12469118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173849","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}
引用次数: 0
Assessing the Reliability of Hysteroscopic Sampling Methods for Diagnosing Atypical Endometrial Hyperplasia. 评估宫腔镜取样方法诊断不典型子宫内膜增生的可靠性。
IF 4.4 2区 医学
Cancers Pub Date : 2025-09-17 DOI: 10.3390/cancers17183036
Luca Giannella, Francesco Piva, Giovanni Delli Carpini, Jacopo Di Giuseppe, Matteo Giulietti, Erica Dugo, Francesco Sopracordevole, Anna Del Fabro, Nicolò Clemente, Barbara Gardella, Giorgio Bogani, Orsola Brasile, Ruby Martinello, Marta Caretto, Alessandro Ghelardi, Gianluca Albanesi, Guido Stevenazzi, Paolo Venturini, Maria Papiccio, Marco Cannì, Maggiorino Barbero, Massimiliano Fambrini, Veronica Maggi, Stefano Uccella, Arsenio Spinillo, Francesco Raspagliesi, Pantaleo Greco, Tommaso Simoncini, Felice Petraglia, Andrea Ciavattini
{"title":"Assessing the Reliability of Hysteroscopic Sampling Methods for Diagnosing Atypical Endometrial Hyperplasia.","authors":"Luca Giannella, Francesco Piva, Giovanni Delli Carpini, Jacopo Di Giuseppe, Matteo Giulietti, Erica Dugo, Francesco Sopracordevole, Anna Del Fabro, Nicolò Clemente, Barbara Gardella, Giorgio Bogani, Orsola Brasile, Ruby Martinello, Marta Caretto, Alessandro Ghelardi, Gianluca Albanesi, Guido Stevenazzi, Paolo Venturini, Maria Papiccio, Marco Cannì, Maggiorino Barbero, Massimiliano Fambrini, Veronica Maggi, Stefano Uccella, Arsenio Spinillo, Francesco Raspagliesi, Pantaleo Greco, Tommaso Simoncini, Felice Petraglia, Andrea Ciavattini","doi":"10.3390/cancers17183036","DOIUrl":"10.3390/cancers17183036","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The diagnosis of atypical endometrial hyperplasia (AEH) is associated with a high rate of concurrent endometrial cancer (EC). This occurrence can be particularly challenging in premenopausal women wishing to become pregnant, as they may be subjected to conservative treatment. The type of endometrial sampling may affect this outcome. Currently, the recommended type of endometrial sampling is under hysteroscopic guidance. There is scant literature regarding the reliability of hysteroscopically guided biopsy (HSC-bio) and hysteroscopic endometrial resection (HSC-res) on this topic. We aimed to assess the underestimation rate of EC in AEH, according to different hysteroscopic sampling methods. The secondary outcome was to evaluate the procedure performance in pre- and postmenopausal women. <b>Methods</b>: We conducted a multi-institutional retrospective study that included 536 women diagnosed with AEH who underwent hysterectomy between 2015 and 2020. Patients were divided into two groups based on the initial diagnostic approach for AEH: HSC-bio and HSC-res. The comparison was performed using univariate and multivariate analyses. <b>Results</b>: 160/536 women (29.9%) showed EC at hysterectomy. Overall, the following rate of EC underestimation was found: HSC-bio = 32.1%, HSC-res = 24.2%, <i>p</i> = 0.07. After adjusting for baseline characteristics using logistic regression analysis, overall, there was no significant association of EC underestimation according to the type of sampling procedure. Interestingly, in premenopausal women, including 161 cases, the rate of EC underestimation in HSC-bio and HSC-res was 28.8% vs. 14.0%, respectively (<i>p</i> = 0.034). <b>Conclusions</b>: There were no significant differences in EC underestimation between the two hysteroscopic procedures in the entire cohort of women with AEH. Limited to the secondary objective, the significant findings in premenopausal women may be of particular clinical interest, as this population may undergo conservative treatment.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173729","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}
引用次数: 0
Application of the STRATCANS Criteria to the MUSIC Prostate Cancer Active Surveillance Cohort: A Step Towards Risk-Stratified Active Surveillance. STRATCANS标准在MUSIC前列腺癌主动监测队列中的应用:迈向风险分层主动监测的一步。
IF 4.4 2区 医学
Cancers Pub Date : 2025-09-17 DOI: 10.3390/cancers17183032
Ana M Moser, Michael Wang, Ava Zamani, Sabir Meah, Stephanie Daignault-Newton, Corinne Labardee, Nicholas Dybas, Jacob Clapper, Brian R Lane, Tudor Borza, Alice Semerjian, Vincent J Gnanapragasam, Kevin B Ginsburg
{"title":"Application of the STRATCANS Criteria to the MUSIC Prostate Cancer Active Surveillance Cohort: A Step Towards Risk-Stratified Active Surveillance.","authors":"Ana M Moser, Michael Wang, Ava Zamani, Sabir Meah, Stephanie Daignault-Newton, Corinne Labardee, Nicholas Dybas, Jacob Clapper, Brian R Lane, Tudor Borza, Alice Semerjian, Vincent J Gnanapragasam, Kevin B Ginsburg","doi":"10.3390/cancers17183032","DOIUrl":"10.3390/cancers17183032","url":null,"abstract":"<p><strong>Background: </strong>The STRATified CANcer Surveillance (STRATCANS) model risk-stratifies patients with prostate cancer (PC) on active surveillance (AS) into three tiers based on their risk of disease progression. We applied STRATCANS to the Michigan Urological Surgery Improvement Collaborative (MUSIC) Prostate registry to assess its association with the risk of biopsy upgrading and time to definitive treatment in a diverse, real-world AS cohort.</p><p><strong>Methods: </strong>We retrospectively reviewed the MUSIC registry for PC patients on AS from 2016 to 2022 and classified patients by STRATCANS tier. Primary outcomes included biopsy upgrading to ≥Grade Group 3 (≥GG3), any biopsy upgrading, and time to definitive treatment.</p><p><strong>Results: </strong>Among 7578 men on AS, 4009, 2732, and 837 patients were in STRATCANS 1, 2, and 3, respectively. The risk of progression to ≥GG3 was 13%, 33%, and 53% for patients in STRATCANS 1, 2, and 3, respectively (<i>p</i> < 0.001). The rate of any biopsy upgrading was approximately 50% at 3 years across all STRATCANS tiers. STRATCANS tiers were also significantly associated with time to definitive treatment, with 16%, 28%, and 35% of men in STRATCANS 1, 2, and 3, respectively, receiving definitive treatment by 36 months. Limitations include confounding inherent to retrospective registry studies, a short 60-month follow-up period, and variability in biopsy method with no centralized pathology and radiology review.</p><p><strong>Conclusions: </strong>STRATCANS has a stepwise association with the risk of progression to ≥GG3 disease and time to definitive treatment among men on AS in the MUSIC cohort, supporting its use as a risk-based, follow-up approach in men on AS.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173741","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}
引用次数: 0
Tumour-Infiltrating Lymphocytes, Tumour Cell Density, and Response to Neoadjuvant Short-Course Radiotherapy in Rectal Cancer: A Translational Sub-Study from the MRC CR07 Clinical Trial. 肿瘤浸润淋巴细胞、肿瘤细胞密度和对直肠癌新辅助短程放疗的反应:来自MRC CR07临床试验的转化亚研究
IF 4.4 2区 医学
Cancers Pub Date : 2025-09-17 DOI: 10.3390/cancers17183040
Jonathan P Callaghan, Ross Jarrett, Alice C Westwood, Jon Laye, Philip Quirke, Derek R Magee, Daniel Bottomley, David Sebag-Montefiore, Lindsay Thompson, Angela Meade, Heike I Grabsch, Nicholas P West
{"title":"Tumour-Infiltrating Lymphocytes, Tumour Cell Density, and Response to Neoadjuvant Short-Course Radiotherapy in Rectal Cancer: A Translational Sub-Study from the MRC CR07 Clinical Trial.","authors":"Jonathan P Callaghan, Ross Jarrett, Alice C Westwood, Jon Laye, Philip Quirke, Derek R Magee, Daniel Bottomley, David Sebag-Montefiore, Lindsay Thompson, Angela Meade, Heike I Grabsch, Nicholas P West","doi":"10.3390/cancers17183040","DOIUrl":"10.3390/cancers17183040","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background&lt;/b&gt;: Rectal cancer is common and frequently treated with neoadjuvant radiotherapy prior to surgery to reduce the risk of tumour recurrence. However, the therapeutic benefits and side effects of radiotherapy can vary between patients, and there are currently no validated biomarkers to predict treatment response. Tumour cell density (TCD) and tumour-infiltrating lymphocyte (TIL) density are proven prognostic biomarkers in colorectal cancer; however, their utility in predicting radiotherapy response remains unclear. We assessed the prognostic and predictive value of TCD and TIL density in rectal cancer patients treated with radiotherapy. &lt;b&gt;Methods&lt;/b&gt;: TCD was quantified using a manual point-counting method in 253 pre-treatment biopsies and across the entire tumour area of 569 resection specimens from the MRC CR07 clinical trial, which randomised patients to either neoadjuvant short-course radiotherapy (SCRT) or straight to surgery (control). TIL density was measured in 102 biopsies and matched resection specimens (73 SCRT, 29 control) across different tumour areas using deep learning-based cell detection in MIM (HeteroGenius Ltd., Leeds, UK). Cutoffs for low/high-TCD and TIL density were both pre-defined and derived from survival data using the survminer R package. Survival analyses were performed to evaluate the predictive and prognostic value of TCD/TIL in relation to overall and cancer-specific survival. &lt;b&gt;Results&lt;/b&gt;: TCD in the resection specimens was lower in the SCRT group (19.9%, IQR 12.9-26.7%) than the control group (34.3%, IQR 27.7-40.5%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). In control resections, low-TCD was associated with a higher risk of all-cause mortality (HR 2.20, 95% CI 1.41-3.44, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) and cancer-related death (HR 2.69, 95% CI 1.41-5.13, &lt;i&gt;p&lt;/i&gt; = 0.0026). In contrast, after SCRT, low resection TCD was associated with a reduced risk of death (HR 0.63, 95% CI 0.40-0.98, &lt;i&gt;p&lt;/i&gt; = 0.04). In the SCRT group, low biopsy TCD prior to radiotherapy was associated with a reduced risk of cancer-related death (HR 0.34, 95% CI 0.13-0.89, &lt;i&gt;p&lt;/i&gt; = 0.028). Across both trial arms, TIL density was higher in pre-treatment biopsies than resections (2492 vs. 1304/mm&lt;sup&gt;2&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Low biopsy TIL density was associated with an increased risk of all-cause mortality (HR 2.43, 95% CI 1.24-4.76, &lt;i&gt;p&lt;/i&gt; = 0.01). The SCRT group had lower TIL density in the resection compared with controls (1210 vs. 1615/mm&lt;sup&gt;2&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), and low resection TIL density across the whole tumour area was associated with a higher risk of death (HR 2.55, 95% CI 1.11-5.87, &lt;i&gt;p&lt;/i&gt; = 0.027). &lt;b&gt;Conclusions&lt;/b&gt;: Our findings support the role of TCD and TIL density as quantitative biomarkers in rectal cancer patients. TCD can be used to assess the degree of response to radiotherapy, and contrasting survival associations are observed between straight-to-surgery and SCRT-treated patients. This study raises the possibility of us","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174066","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}
引用次数: 0
Comparing the Perioperative and Oncological Outcomes of Open Versus Minimally Invasive Inguinal Lymphadenectomy in Penile Cancer: A Systematic Review and Meta-Analysis. 比较开放式与微创腹股沟淋巴结切除术治疗阴茎癌的围手术期和肿瘤预后:系统回顾和荟萃分析。
IF 4.4 2区 医学
Cancers Pub Date : 2025-09-17 DOI: 10.3390/cancers17183035
Yu Guang Tan, Khi Yung Fong, Nathanael Kai-Jun Goh, Alvin Ym Lee, Kae Jack Tay, John Sp Yuen, Michael R Abern, Kenneth Chen
{"title":"Comparing the Perioperative and Oncological Outcomes of Open Versus Minimally Invasive Inguinal Lymphadenectomy in Penile Cancer: A Systematic Review and Meta-Analysis.","authors":"Yu Guang Tan, Khi Yung Fong, Nathanael Kai-Jun Goh, Alvin Ym Lee, Kae Jack Tay, John Sp Yuen, Michael R Abern, Kenneth Chen","doi":"10.3390/cancers17183035","DOIUrl":"10.3390/cancers17183035","url":null,"abstract":"<p><strong>Background: </strong>Long-term survival in penile cancer is dependent on the presence and extent of lymph node metastases. Historically, inguinal lymph node dissection (ILND) has been performed via an open approach (O-ILND). More recently, minimally invasive surgical alternatives (MIS-ILND) such as video-endoscopic and robot-assisted ILND have emerged. This review aims to compare the (1) perioperative outcomes, (2) complication rates, and (3) oncological efficacy between O-ILND and MIS-ILND.</p><p><strong>Methods: </strong>We conducted a PRISMA-compliant meta-analysis including studies comparing O-ILND versus MIS-ILND for penile cancer. Outcomes were pooled in random-effects meta-analyses.</p><p><strong>Results: </strong>Sixteen articles comprising 1054 patients were analysed. There was an observed trend towards longer operative time for the MIS-ILND approach (mean difference 28 min; 95% CI -2 to 58 min, <i>p</i> = 0.06), particularly with the robotic-assisted technique. Total LN yield (mean 12.3, mean difference 0.3, 95% CI -0.3 to 0.9, <i>p</i> = 0.13), and positive LN (RR 0.98, 95% CI 0.88-1.10, <i>p</i> = 0.75) were similar between groups. MIS-ILND significantly reduced complication rates for both minor (RR: 0.65, 95% CI 0.45-0.94, <i>p</i> = 0.02) and major complications (RR: 0.25, 95% CI 0.12-0.53, <i>p</i> = 0.002). Particularly, there was also lower wound infection rate with MIS-ILND (RR: 0.43, 95% CI 0.22-0.82, <i>p</i> = 0.02), corresponding to a shorter hospital stay of average 4 days (MD -4, 95% CI -6--2, <i>p</i> = 0.05). Rates of skin/flap necrosis, lymphedema, lymphocele, and drainage time did not differ significantly. Local groin recurrence and overall survival did not differ between approaches.</p><p><strong>Conclusions: </strong>MIS-ILND is associated with fewer perioperative complications and shorter hospitalisation without compromising oncologic outcomes. These findings support its broader adoption, particularly in high-volume centres with appropriate surgical expertise.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172920","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}
引用次数: 0
Protein and Peptide in Cancer Research: From Biomarker to Biotherapeutics. 癌症研究中的蛋白质和肽:从生物标志物到生物疗法。
IF 4.4 2区 医学
Cancers Pub Date : 2025-09-17 DOI: 10.3390/cancers17183031
Joo Hyeong Seo, Seung Hoon Shin, Hye Rin Woo, Yu Rim An, A Hyun Youn, Song Yeon Kim, Mi-Ran Ki, Seung Pil Pack
{"title":"Protein and Peptide in Cancer Research: From Biomarker to Biotherapeutics.","authors":"Joo Hyeong Seo, Seung Hoon Shin, Hye Rin Woo, Yu Rim An, A Hyun Youn, Song Yeon Kim, Mi-Ran Ki, Seung Pil Pack","doi":"10.3390/cancers17183031","DOIUrl":"10.3390/cancers17183031","url":null,"abstract":"<p><p>Proteins and peptides play a pivotal role in key pathological processes, including cancer growth, immune evasion, angiogenesis, and metastasis. Consequently, they are gaining attention as significant biomolecules in the diagnosis and treatment of various diseases. This review provides a comprehensive overview of the latest research trends and technological advancements in protein- and peptide-based cancer diagnostic and therapeutic strategies. It covers the clinical application of major diagnostic markers such as PSA, CA125, HER2, and AFP, as well as therapeutic strategies including monoclonal antibodies, immune checkpoint inhibitors, and anticancer peptides. Additionally, it introduces quantitative analysis techniques such as ELISA, mass spectrometry, and CyTOF, as well as advancements in delivery systems based on nanoparticle-peptide complexes. Peptides offer advantages for precision therapy due to their high target specificity and structural modifiability. However, they also have limitations such as stability, enzymatic degradation, and delivery efficiency. Emerging technologies such as synthetic biology, computational design, and omics-integrated analysis are being developed to address these challenges, and rapid advancements in this field are enhancing the potential for clinical application. This review underscores the potential of protein- and peptide-based strategies for precision cancer diagnosis and personalized therapy and proposes future research directions in this field.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173602","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}
引用次数: 0
Immune Checkpoint Inhibitor Use in Advanced Hepatocellular Carcinoma: A Real-World Analysis of Efficacy and Toxicity. 免疫检查点抑制剂在晚期肝细胞癌中的应用:疗效和毒性的真实世界分析。
IF 4.4 2区 医学
Cancers Pub Date : 2025-09-17 DOI: 10.3390/cancers17183034
Fode Tounkara, Deepak Sherpally, Khalid Mumtaz, Mina S Makary, Russell F Palm, Ashish Manne
{"title":"Immune Checkpoint Inhibitor Use in Advanced Hepatocellular Carcinoma: A Real-World Analysis of Efficacy and Toxicity.","authors":"Fode Tounkara, Deepak Sherpally, Khalid Mumtaz, Mina S Makary, Russell F Palm, Ashish Manne","doi":"10.3390/cancers17183034","DOIUrl":"10.3390/cancers17183034","url":null,"abstract":"<p><strong>Background: </strong>While immune checkpoint inhibitors (ICIs) have redefined systemic therapy in hepatocellular carcinoma (HCC), pivotal trials have not yet included patients with advanced liver disease. Real-world data are needed to assess treatment outcomes in advanced liver disease populations.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of 53 HCC patients treated with ICIs at a large single center between January 2017 and June 2023. Clinical characteristics, liver function scores [Child-Turcotte-Pugh (CTP) and albumin-bilirubin (ALBI)], treatment history, and survival outcomes were analyzed. Primary endpoints included progression-free survival (PFS), survival from ICI initiation (OS-ICI), and overall survival (OS). Secondary endpoints included incidence and predictors of immune-related adverse events (irAEs).</p><p><strong>Results: </strong>Among 53 HCC patients treated with ICIs, the median OS, OS-ICI, and PFS were 18.7 months (m), 7.4 m, and 4.6 m, respectively. On multivariable analysis, a higher ALBI grade and history of alcohol use were independently associated with worse PFS and OS-ICI, while prior locoregional therapy (LRT) significantly improved OS (HR: 0.43; <i>p</i>: 0.012). The ALBI grade outperformed the CTP score in predicting outcomes, highlighting its utility as a more objective liver function marker. Patients receiving atezolizumab-bevacizumab showed improved OS-ICI compared to other regimens (HR: 0.37; <i>p</i> = 0.021). irAEs occurred in 19% of patients, most commonly in those with CTP-A, and were generally manageable.</p><p><strong>Conclusions: </strong>These real-world insights into the efficacy and safety of ICI-based therapies across a more diverse HCC population are usually not represented in clinical trials.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173573","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}
引用次数: 0
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