Cancer Medicine最新文献

{"title":"Cancer Accumulation and Anticancer Activity of “CROX (Cluster Regulation of RUNX)” PIP in HER2-Positive Gastric Cancer Evaluated by Chicken Egg Cancer Model","authors":"Tatsuya Masuda,&nbsp;Takayoshi Watanabe,&nbsp;Yasutoshi Tatsumi,&nbsp;Jason Lin,&nbsp;Kazuhiro Okumura,&nbsp;Toshinori Ozaki,&nbsp;Hiroshi Sugiyama,&nbsp;Yasuhiko Kamikubo","doi":"10.1002/cam4.70845","DOIUrl":"https://doi.org/10.1002/cam4.70845","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>We have focused on pyrrole-imidazole (PI) polyamide compounds, which preferentially bind to their target DNA sequences. To validate our “CROX (Cluster Regulation of RUNX)” strategy, we have created a novel PI polyamide-based inhibitor against RUNX termed Chb-M’. Recently, we have confirmed its cancer-specific uptake in mouse xenograft derived from <i>HER2</i>-positive gastric cancer cells. The accumulation and efficacy of Chb-M' in cancer has not yet been investigated <i>in vivo</i>, which is a simpler and less expensive method other than mouse xenograft models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In the present study, we have employed the simple and versatile experimental system termed CAM (chorioallantoic membrane) model, and evaluated whether Chb-M’ could have the cancer accumulation potential and anti-cancer activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Based on our present results, gastric cancer MKN45 cells transplanted onto CAM successfully developed cancers, and the intravenously injected FITC-labeled Chb-M’ obviously accumulated in these CAM cancers. As expected, the treatment of the CAM cancers with Chb-M’ significantly attenuated the growth of the CAM cancers. Our present results were basically identical to those obtained from mouse xenograft model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our present findings strongly suggest that Chb-M’ preferentially accumulates in cancer to suppress its growth, and the CAM model might serve as a valuable and promising platform to rapidly assess the cancer uptake and anti-cancer efficacy of various PI polyamide-based drug candidates.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70845","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749849","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":"METTL3, an Independent Adverse Prognostic Factor for AML, Promotes the Development of AML by Modulating the PGC-1α–MAPK Pathway and PGC-1α–Antioxidant System Axis","authors":"Yuqian Tang,&nbsp;Xiaoyan Liu,&nbsp;Wu Ye,&nbsp;Xiaojia Wang,&nbsp;Xiaoyu Wei,&nbsp;Yiwen Du,&nbsp;Ying Zhang,&nbsp;Yuping Gong","doi":"10.1002/cam4.70771","DOIUrl":"https://doi.org/10.1002/cam4.70771","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>m⁶A represents a prevalent epigenetic modification of mammalian mRNAs. Studies have demonstrated that m⁶A RNA methylation-modifying enzymes play crucial roles in the onset and progression of AML. However, their clinical relevance remains undefined, and the mechanisms underlying their modulation of AML have yet to be elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The expression levels of the m⁶A RNA-modifying enzymes METTL3, METTL14, WTAP, FTO and ALKBH5 were elevated in AML patients. METTL3-positive AML is often accompanied by DNMT3A mutations and is also an independent poor prognostic factor for AML patients. Following METTL3 knockdown, we observed a decrease in the m⁶A level of the mitochondrial oxidative stress gene PGC-1α in K562 and MV4-11 cells. We analyzed the expression levels of PGC-1α and METTL3 mRNA in 105 patients with primary AML. The expression levels of PGC-1α and METTL3 mRNA were positively correlated. Similar to METTL3 knockdown, PGC-1α gene knockdown resulted in increased phosphorylation of the key signaling molecules P38, c-Jun and ERK1/2 in the MAPK signaling pathway, and decreased mRNA levels of SOD1, GPX1, catalase and UCP2 in the antioxidant system of K562 cells. Analysis of the TCGA and GSE13159 datasets, along with samples from West China Hospital, revealed that patients exhibiting high PGC-1α expression had a poor prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The m⁶A methylation-modifying enzyme METTL3 is an independent prognostic factor for poor prognosis in AML patients. PGC-1α is a downstream signaling molecule of METTL3, and METTL3 affects its expression by regulating the m⁶A level of PGC-1α. PGC-1α acts as an oncogene in AML by affecting the MAPK pathway and antioxidant system.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70771","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749852","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":"Role of SIRT7 in Prostate Cancer Progression: New Insight Into Potential Therapeutic Target","authors":"Jiale Zhang,&nbsp;Chenxin Liu,&nbsp;Wenting Luo,&nbsp;Baoqing Sun","doi":"10.1002/cam4.70786","DOIUrl":"https://doi.org/10.1002/cam4.70786","url":null,"abstract":"<p>Prostate cancer (PCa) is the second most common cancer in men worldwide, and understanding its molecular mechanisms is crucial for developing effective treatment strategies. SIRT7, a NAD+-dependent histone deacetylase, has emerged as a key regulator in PCa progression due to its roles in chromatin remodeling, DNA repair, and transcriptional regulation. Analysis of 492 PCa samples from The Cancer Genome Atlas (TCGA) via cBioPortal revealed that high SIRT7 expression is associated with poor prognosis in PCa patients. Mechanistically, SIRT7 deacetylates histone H3 at lysine 18 (H3K18Ac), a marker associated with aggressive tumors, suppressing tumor suppressor genes and promoting cancer cell proliferation and survival. Epithelial-mesenchymal transition (EMT) is a cellular biological process in which epithelial cells undergo specific molecular and morphological changes to transform into cells with characteristics of mesenchymal cells. SIRT7 also regulates EMT, and inhibiting SIRT7 in PCa cell lines reduces cell migration and invasion, highlighting its potential as a therapeutic target. In summary, the clinical significance of SIRT7 expression in PCa requires further research to elucidate its mechanisms. Developing specific inhibitors targeting SIRT7's deacetylase activity is a promising therapeutic strategy. SIRT7 plays a crucial role in regulating biological processes such as cell proliferation, cell cycle, and apoptosis in PCa through its epigenetic control of gene expression and maintenance of genomic stability. Therefore, SIRT7 may be a potential therapeutic target for PCa, and its expression could have prognostic value for PCa patients, providing important guidance for clinical monitoring and diagnosis by physicians.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70786","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741329","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":"Predictors of Transplant Regret: A Case–Control Study Nested Within a Prospective Cohort of HSCT Recipients","authors":"Janae L. Kirsch,&nbsp;James R. Cerhan,&nbsp;William J. Hogan,&nbsp;Holly C. Edwards,&nbsp;Christi A. Patten,&nbsp;Tabetha Brockman,&nbsp;Christine Hughes,&nbsp;Angela Dispenzieri,&nbsp;Stephen M. Ansell,&nbsp;Dennis A. Gastineau,&nbsp;Shawna L. Ehlers","doi":"10.1002/cam4.70828","DOIUrl":"https://doi.org/10.1002/cam4.70828","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To explore pre–hematopoietic stem cell transplant (HSCT) demographic, disease, and psychological factors predictive of future transplant regret and to determine post-HSCT variables associated with regret.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Methods</h3>\u0000 \u0000 <p>HSCT candidates participated in a prospective cohort study (June 2008–October 2013) examining health behaviors and HSCT outcomes, including completion of standardized surveys at pre-HSCT (baseline) and 1-year post-HSCT. Cases were participants that endorsed regret at 1-year post-HSCT follow-up, and controls were participants without regret at 1 year, matched on age, sex, and transplant type. For cases and controls, pre-HSCT psychosocial evaluations were abstracted from the electronic health record and coded to determine the Psychosocial Assessment of Candidates for Transplantation score, psychosocial stressors, and mental health diagnoses. The association of selected factors with regret was estimated with odds ratios and 95% confidence intervals from conditional logistic regression models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At post-HSCT, 49 participants of 638 endorsed transplant regret (8%) and formed the case group; 98 controls were matched from remaining participants. Cases and controls were well matched on age (56.6 vs. 57.2 years), sex (both groups 34.7% female), and transplant type (both groups 81.6% autologous). After controlling for the number of hospitalizations and active treatment status, conditional logistic regression revealed that patients who endorsed regret were 3.7 times (95% CI = 1.37–9.69, <i>p</i> = 0.008) more likely to not be in remission compared to controls at 1-year post-HSCT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Matched case–control analyses revealed that no pre-HSCT variables collected during the pre-HSCT evaluation period were predictive of transplant regret, while poorer outcomes at 1-year after transplant were associated with regret.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70828","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741270","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":"Detecting PI3K and TP53 Pathway Disruptions in Early-Onset Colorectal Cancer Among Hispanic/Latino Patients","authors":"Cecilia Monge,&nbsp;Brigette Waldrup,&nbsp;Sophia Manjarrez,&nbsp;Francisco G. Carranza,&nbsp;Enrique Velazquez-Villarreal","doi":"10.1002/cam4.70791","DOIUrl":"https://doi.org/10.1002/cam4.70791","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/Objectives</h3>\u0000 \u0000 <p>This study aims to characterize PI3K and TP53 pathway alterations in Hispanic/Latino patients with early-onset colorectal cancer (CRC), focusing on potential differences compared to non-Hispanic White patients. Understanding these differences may shed light on the molecular basis of CRC health disparities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using cBioPortal, we conducted a bioinformatics analysis to evaluate CRC mutations within the PI3K and TP53 pathways. CRC patients were stratified by age and ethnicity: (1) early-onset (&lt; 50 years) versus late-onset (≥ 50 years) and (2) early-onset in Hispanic/Latino patients compared to early-onset in non-Hispanic White patients. Mutation frequencies were assessed using descriptive statistics, with chi-squared tests comparing proportions between early-onset Hispanic/Latino and non-Hispanic White groups. Kaplan–Meier survival curves were generated to assess overall survival for early-onset Hispanic/Latino patients, stratified by the presence or absence of PI3K and TP53 pathway alterations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant differences were noted when comparing early-onset CRC in Hispanic/Latino patients to early-onset CRC in non-Hispanic White patients. PI3K (47.1% vs. 35.2%, <i>p</i> = 9.39e-3) and TP53 (89.1% vs. 81.7%, <i>p</i> = 0.04) pathway alterations were more prevalent in early-onset CRC among Hispanic/Latino patients, with AKT1 (5.1% vs. 1.8%, <i>p</i> = 0.03), INPP4B (4.3% vs. 1.4%, <i>p</i> = 0.04), and TSC1 (7.2% vs. 3.1% <i>p</i> = 0.03) gene alterations also significantly higher in this group. Significant differences were observed in TP53 mutations between colon adenocarcinomas (90% vs. 79.1%, <i>p</i> = 0.03), with higher prevalence in Hispanic/Latino patients when stratified by tumor site. No significant differences were observed between early-onset and late-onset CRC patients within the Hispanic/Latino cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings highlight the distinct role of PI3K and TP53 pathway disruptions in early-onset CRC among Hispanic/Latino patients, suggesting that pathway-specific mechanisms may drive cancer health disparities. Insights from this study could inform the potential development of precision medicine approaches and targeted therapies aimed at addressing these disparities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741330","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":"A Population-Based Study of Infectious Diseases Mortality Risk in Patients With Hematologic Malignancies 2000–2020","authors":"Wenshuai Zheng,&nbsp;Shenyu Wang,&nbsp;Bo Peng,&nbsp;Xiaoning Gao","doi":"10.1002/cam4.70850","DOIUrl":"https://doi.org/10.1002/cam4.70850","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with hematologic malignancies are at high risk of dying from infectious diseases. However, little attention has been paid to infectious diseases mortality (IDM) in these patients. The aim of our study is to determine the incidence and trends of IDM in patients with hematologic malignancies, identify risk factors associated with IDM, and compare the risk of IDM in patients with the general United States population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The data of patients with hematologic malignancies between 2000 and 2020 was retrieved from the Surveillance, Epidemiology, and End Results program. Standardized mortality ratios (SMRs) and IDM rates were calculated. A competing risk model was performed to identify potential risk factors of IDM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 700,678 patients, 15,028 IDM were identified with an IDM rate of 401.31/100,000 person-years. Compared with the general population, the SMR of IDM was 3.34, and the elevated risk of IDM ran through the follow-up period. For all cancer subtypes, the IDM rates were highest in the first 2 months after diagnosis and gradually declined thereafter. For all patients, the early period of diagnosis, older age, male, non-Hispanic black, single or divorced/separated/widowed status, no chemotherapy, and no radiation were risk factors for IDM. For patients with Hodgkin lymphoma or non-Hodgkin lymphoma, advanced stage was also a risk factor for IDM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Given the high risk of IDM in patients with hematologic malignancies, it is extremely important to identify patients at high risk of IDM and provide timely intervention to prevent early death from infections and improve prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70850","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741266","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":"Prediction of Sleep Quality in Cancer Survivors Based on Arousal, Pain, and Worry: The Mediating Role of Dysfunctional Beliefs and Attitudes About Sleep","authors":"Omid Amani,&nbsp;Mohammad Ali Mazaheri,&nbsp;Mona Malekzadeh Moghani,&nbsp;Fariba Zarani","doi":"10.1002/cam4.70773","DOIUrl":"https://doi.org/10.1002/cam4.70773","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Our study explores the prevalence, severity, and psychological correlates of insomnia in cancer survivors, aiming to predict sleep quality based on pre-sleep arousal, pain, and worry, while examining the mediating role of dysfunctional beliefs and attitudes about sleep (DBAS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A descriptive-correlational design was employed, with 200 cancer survivors from Tehran, Iran, selected through convenience sampling in 2022. Participants completed the Pittsburgh Sleep Quality Index (PSQI), Chronic Pain Grade (CPG), Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS), Pennsylvania Worry Questionnaire (PSWQ), and Pre-Sleep Arousal Scale (PSAS). The data were analyzed using correlation and multiple regression through SPSS-23 software.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>On average, 37.07 months post-treatment, 95% of survivors reported delayed sleep onset, 88.5% frequent awakenings, 72% reduced sleep duration, and 67% morning dysfunction. Significant positive associations were found between pre-sleep arousal, chronic pain (<i>r</i> = 0.552), worry (<i>r</i> = 0.161), DBAS (<i>r</i> = 0.363), and poor sleep quality (<i>r</i> = 0.607). Regression analysis indicated that physical arousal (<i>B</i> = 0.29, <i>p</i> = 0.01) and DBAS (<i>B</i> = 0.14, <i>p</i> &lt; 0.05) were significant predictors of sleep quality, with DBAS mediating the relationship between physical arousal and sleep quality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Persistent sleep problems after cancer treatment highlight the need for targeted interventions in survivorship care. Sleep-focused strategies may improve sleep quality and reduce the burden of insomnia-related issues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Implications for Cancer Survivors</h3>\u0000 \u0000 <p>Addressing pre-sleep arousal, pain, worry, and DBAS through targeted interventions is crucial for improving sleep quality and overall quality of life in cancer survivors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70773","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741272","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":"Central Nervous System Prophylaxis Approach in High-Risk Diffuse Large B-Cell Lymphoma Patients: A Retrospectively Collected, Single-Center Cohort Analysis","authors":"Yanli Wang,&nbsp;Xiaolian Wen,&nbsp;Tao Guan,&nbsp;Hongwei Zhang,&nbsp;Wei'e Han,&nbsp;Min Bai,&nbsp;Xiaolan Liu,&nbsp;Min Zhang,&nbsp;Liping Su,&nbsp;Weihua Zhang","doi":"10.1002/cam4.70830","DOIUrl":"https://doi.org/10.1002/cam4.70830","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Recent advances in the prevention of diffuse large B-cell lymphoma (DLBCL) have considerably focused on optimal strategies for preventing its recurrence in the central nervous system (CNS) in patients. This retrospective study aimed to assess the protective efficacy of intravenous high-dose methotrexate (HD-MTX) regimens in newly diagnosed patients with DLBCL presenting a high risk for CNS recurrence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 136 newly diagnosed high-risk DLBCL patients (HD-MTX group: <i>n</i> = 46; non-HD-MTX group: <i>n</i> = 90) were enrolled in this retrospective study. The primary endpoints included CNS recurrence rate, progression-free survival (PFS), overall survival (OS), and toxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The 2-year CNS recurrence rates (median follow-up period: 25.5 months; 95% confidence interval: 21.0–30.0) were 4.3% and 11.1% in the HD-MTX and non-HD-MTX groups (<i>p</i> = 0.337), respectively. Additionally, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 70.7% versus 60.8% and 72.9% versus 60.8% (<i>p</i> = 0.013 and <i>p</i> = 0.024), respectively. The subgroup analysis for PFS and OS revealed that patients classified as the National Comprehensive Cancer Network (NCCN)—International Prognostic Index (IPI) low- or intermediate-risk, at a younger age, and without B symptoms demonstrated potential benefits from the HD-MTX treatment. In total, 46 patients completed 92 cycles of HD-MTX treatment, of which, 49 cycles were administered on day 6 of the R-CHOP regimen, with an average delay of no more than 4 days. In contrast, the remaining 43 cycles were initiated on days 10–14 following the completion of the R-CHOP regimen, with an average delay of 15 days. Interestingly, the incidence of hematological or non-hematological toxicity did not differ significantly among the groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Owing to the lack of robust evidence, the role of HD-MTX in preventing CNS recurrence could not be conclusively determined. Nevertheless, some patients could tolerate the treatment, such as younger individuals and those at NCCN-IPI low or intermediate risk, suggesting the efficacy of intravenous HD-MTX administration on day 6 as an optimal strategy for preventing CNS recurrence of DLBCL.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70830","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741331","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":"Phase II Study of Nivolumab and Ipilimumab for Treatment of Metastatic/Recurrent Adenoid Cystic Carcinoma (ACC) of all Anatomic Sites of Origin and Other Malignant Salivary Gland Tumors","authors":"Young Kwang Chae,&nbsp;Richard Duan,&nbsp;Liam Il-Young Chung,&nbsp;Youjin Oh,&nbsp;Borislav Alexiev,&nbsp;Sangwon Shin,&nbsp;Sukjun Kim,&nbsp;Irene Helenowski,&nbsp;Maria Matsangou,&nbsp;Victoria Villaflor,&nbsp;Devalingam Mahalingam","doi":"10.1002/cam4.70724","DOIUrl":"https://doi.org/10.1002/cam4.70724","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Dual checkpoint inhibitor therapy with nivolumab and ipilimumab has been FDA approved for a number of cancer sites. However, its role in the treatment of ACC and non-ACC salivary gland carcinomas (non-ACC SGC) is not well established.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Analysis</h3>\u0000 \u0000 <p>We performed Simon's two-stage prospective single-institution Phase II clinical trial of nivolumab with ipilimumab. Two cohorts were analyzed: patients with metastatic/recurrent ACC and patients with non-ACC SGC. The primary endpoint was median progression-free survival (PFS); secondary endpoints were overall response rate (ORR), overall survival (OS), and toxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patient enrollment was prematurely terminated due to funding constraints. In total, 19 patients with ACC and 5 patients with non-ACC SGC were enrolled. The patients with ACC had a median OS of 30.0 months (95% CI 15.3-NR months), a median PFS of 8.3 months (95% CI 5.5–30.0 months), and a disease control rate (DCR) of 53% (10/19). The ORR in the ACC group was 5% (CR 0%, <i>n</i> = 0; confirmed PR 5%, <i>n</i> = 1), with one patient having continued stable disease at the time of trial conclusion. The patients with non-ACC SGC had a median OS of 10.4 months (95% CI 6.21-NR months), a median PFS of 6.21 months (95% CI 2.83-NR months), and a DCR of 40% (2/5). The ORR in this cohort was 0%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In patients with recurrent or metastatic ACC and non-ACC SGC, the combination of nivolumab with ipilimumab resulted in moderate disease control. Further studies are warranted to validate our findings.</p>\u0000 \u0000 <p>Trial number: NCT03146650.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70724","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741269","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":"A Prospective, Multicenter Analysis of Recurrence-Free Survival After Sentinel Lymph Node Biopsy Decisions Influenced by the 31-GEP","authors":"J. Michael Guenther,&nbsp;Andrew Ward,&nbsp;Brian J. Martin,&nbsp;Mark Cripe,&nbsp;Timothy Beard,&nbsp;Oliver Wisco,&nbsp;Rohit Sharma,&nbsp;Stanley P. Leong,&nbsp;Richard Essner,&nbsp;Joseph I. Clark,&nbsp;John Hamner,&nbsp;Brenda Sickle-Santanello,&nbsp;Maki Yamamoto","doi":"10.1002/cam4.70839","DOIUrl":"https://doi.org/10.1002/cam4.70839","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although most patients with cutaneous melanoma (CM) will have a negative sentinel lymph node biopsy (SLNB), up to 20%–30% of these patients will recur. The 31-gene expression profile (31-GEP) test has been prospectively validated to identify patients at low (Class 1A), intermediate (Class 1B/2A), and high (Class 2B) risk of SLN positivity and recurrence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>DECIDE is a prospective, multicenter study to assess the effect of 31-GEP testing on SLNB performance rates in patients with T1–T2 tumors considering SLNB and to study long-term outcomes. Here, we assessed outcomes in patients with a Class 1A 31-GEP result (<i>n</i> = 130).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of Class 1A patients, 63 had an SLNB, with a 3.2% SLN positivity rate (2/63). No Class 1A patients, regardless of SLN status, experienced a recurrence (2-year median follow-up).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results are consistent with previous studies that showed the 31-GEP can identify patients at low risk of SLN positivity and recurrence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70839","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741271","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}