Cancer Medicine最新文献

{"title":"Transarterial Chemoembolization With or Without Systemic Therapy for Unresectable Hepatocellular Carcinoma: A Retrospective Comparative Study","authors":"Chengxiang Guo,&nbsp;Weiran Du,&nbsp;Yiwen Chen,&nbsp;Wenbo Xiao,&nbsp;Ke Sun,&nbsp;Yan Shen,&nbsp;Min Zhang,&nbsp;Jian Wu,&nbsp;Shunliang Gao,&nbsp;Jun Yu,&nbsp;Risheng Que,&nbsp;Xing Xue,&nbsp;Xueli Bai,&nbsp;Tingbo Liang","doi":"10.1002/cam4.70633","DOIUrl":"10.1002/cam4.70633","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Standard treatments provide limited benefits for patients with intermediate- or advanced-stage hepatocellular carcinoma (HCC). This retrospective observational study aimed to assess the potential improvements in outcomes associated with systemic therapies in patients receiving transarterial chemoembolization (TACE) for initially unresectable HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Between February 2019 and March 2023, we reviewed patients diagnosed with intermediate-to-advanced HCC who were treated with either TACE or TACE combined with antiangiogenic agents and immune checkpoint inhibitors (combination therapy) as their initial treatment. To address potential confounding biases, patients were further stratified into surgical and non-surgical cohorts, and separate analyses were conducted. The primary endpoints were progression-free survival (PFS) and overall survival (OS), with safety profiles also evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 279 patients with initially unresectable intermediate or advanced HCC, 156 successfully underwent curative-intent liver resection after preoperative treatments (TACE group, <i>n</i> = 69; combination group, <i>n</i> = 87), while 123 patients continued with non-surgical treatments (TACE group, <i>n</i> = 31; combination group, <i>n</i> = 92). After propensity score matching, 26 matched patient pairs were generated within the non-surgical cohort. The combination group exhibited significantly improved PFS in non-surgical patients compared with the TACE group (9.4 vs. 7.2 months, <i>p</i> = 0.043). Cox proportional hazards analysis further confirmed that combination therapy was associated with improved PFS (hazard ratio = 0.476, 95% confidence interval: 0.257–0.883, <i>p</i> = 0.019). For surgical patients exceeding the up-to-seven criteria, the combination group demonstrated superior median PFS (18.0 vs. 14.6 months, <i>p</i> = 0.03) and OS (not reached vs. 50.1 months, <i>p</i> = 0.049) compared with the TACE group. Adverse events were manageable, with no treatment-related fatalities reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Combination therapy with TACE demonstrated enhanced survival benefits for patients with intermediate to advanced HCC, particularly in surgical patients with higher tumor burdens.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70633","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187834","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":"Inflammatory/Immune Adverse Events in Chronic Myeloid Leukemia Patients During Treatment With Bosutinib","authors":"E. Agostani,&nbsp;E. Tassistro,&nbsp;L. Antolini,&nbsp;C. Gambacorti-Passerini","doi":"10.1002/cam4.70580","DOIUrl":"https://doi.org/10.1002/cam4.70580","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Bosutinib, a tyrosine kinase inhibitor (TKI), is effective in treating chronic myeloid leukemia (CML) patients resistant or intolerant to previous TKIs. Unlike other TKIs, bosutinib's lack of inhibition of c-KIT and PDGFR may contribute to its unique tolerability profile. Similar to dasatinib, it targets Bcr/Abl and SRC kinases, particularly Lyn, raising safety concerns. In fact, the susceptibility of Lyn −/− mice to autoimmune disorders and the deregulation of Lyn-dependent pathways in patients with lupus were previously shown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to assess the time-adjusted rate (TAR) of inflammatory/immune-related adverse events in bosutinib-treated patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed clinical data from 60 patients with a minimum follow-up of three months. We used the CTCAE dictionary to identify immune-related adverse events (irAEs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients had a median treatment duration of 47.9 months (IQR: 38.4–121.8), totaling 592.7 person-months. Among 33 patients (55% of the sample), we detected 94 irAEs (2.3% of total adverse events), including giant cell arteritis, psoriasis, erythema nodosum, articular pain, pleural and pericardial effusion, and three cases of recurrent sterile pneumonia. The estimated TAR of the first irAEs was 14.7 (95% CI: 10.4–20.7) events per 100 person-years; considering repeated irAEs, the TAR was 28.4 (95% CI: 23.2–34.8) events per 100 person-years. The median time to the first irAE was 14.8 months (IQR: 7.1–42). These rates are higher than those observed in imatinib-treated patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings support the clinical impression of a high incidence of irAEs in bosutinib-treated patients and may lead to an enhanced understanding of bosutinib's safety profile and mechanism of action.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70580","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248575","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":"Trends in the Incidence and Survival Outcomes in Patients With Small Cell Lung Cancer in the United States: An Analysis of the SEER Database","authors":"Dipesh Uprety,&nbsp;Randell Seaton,&nbsp;Abesh Niroula,&nbsp;Tarik Hadid,&nbsp;Kaushal Parikh,&nbsp;Julie J. Ruterbusch","doi":"10.1002/cam4.70608","DOIUrl":"https://doi.org/10.1002/cam4.70608","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There has been a lack of updated epidemiological data on the incidence and survival outcomes for patients with small cell lung cancer (SCLC) in the United States over the last two decades.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective, population-based study was conducted utilizing the Surveillance, Epidemiology, and End Results (SEER) program to identify patients with SCLC from 2000 to 2020. Trends in cancer incidence, incidence-based mortality rates, 1-year relative survival rates and 1-year observed survival were evaluated utilizing the SEER database.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The database identified a total of 188,426 SCLC patients during the study period from 2000 through 2020. The age-adjusted incidence rate slowly declined, on average, by 3% (95% CI: −3.2% to −2.8%) each year from 9 per 100,000 in 2000 to 4.6 per 100,000 in 2020. The decline is evident for all age groups, sexes, and races. Incidence-based mortality also declined slowly from 6.6 in 2005 to 3.5 in 2020. However, survival outcomes, including 1-year relative survival and 1-year observed survivals, have not improved significantly over the last two decades.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study found that the incidence of SCLC has decreased from 2000 to 2020, likely due to a reduction in smoking rates, underscoring the importance of smoking abstinence. An improvement in incidence-based mortality is likely related to an enhanced medical care and a decrease in the incidence of SCLC, but the lack of improvement in survival outcomes reflects the need for more effective systemic therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70608","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248577","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":"Utilization of Radical Prostatectomy Versus Radiation Therapy for Gleason Grade Group 5 Prostate Cancer Before and After USPSTF Grade D Recommendation Against Prostate-Specific Antigen Screening in 2012","authors":"H. Scott McGinnis,&nbsp;Taylor Corriher,&nbsp;James Janopaul-Naylor,&nbsp;Subir Goyal,&nbsp;Yuan Liu,&nbsp;Zelin Wang,&nbsp;Sagar A. Patel","doi":"10.1002/cam4.70624","DOIUrl":"https://doi.org/10.1002/cam4.70624","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The 2012 United States Preventive Services Task Force (USPSTF) Grade D recommendation against prostate-specific antigen (PSA) screening has resulted in a shift to higher-stage prostate cancer (PC) at diagnosis. We evaluate the utilization of radical prostatectomy (RP) versus radiation therapy (RT) in the US for Gleason grade group 5 (GG5) prostate cancer before and after 2012.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We identified 34,011 men with localized GG5 PC undergoing primary therapy with (1) RP or (2) RT + androgen deprivation therapy (ADT) between 2004 and 2017 from the National Cancer Database. The chi-square test was used to compare the relative use of RP and RT before versus after 2012. Annual use of RP versus RT from 2004 to 2017 was compared using Cochran-Armitage test for trend. We modeled the effect of treatment year on the use of RP using multivariable logistic regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Across all centers, the use of RP increased from 31% to 41% (<i>p</i> for trend &lt; 0.001). 2012 was associated with significant inflection for increase in RP use in all centers. There was an increased odds of receiving RP after 2012 (adjusted OR 1.34, 95% CI 1.28–1.40, <i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Utilization of RP for GG5 PC has significantly increased in the United States over the past decade. It remains unknown if outcomes may be compromised in this group of high-risk men, many of whom require post-prostatectomy RT and/or ADT. Prospective comparison of RP versus RT + ADT for GG5 PC are needed to determine optimal treatment for these patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70624","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248578","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":"Genetic Characterization of the Immortalized Human Nasopharyngeal Carcinoma Cell Line NPC/HK1","authors":"Anna Makowska,&nbsp;Udo Kontny,&nbsp;Josef van Helden,&nbsp;Barbara Hildebrandt,&nbsp;Herdit M. Schüler,&nbsp;Ralf Weiskirchen","doi":"10.1002/cam4.70422","DOIUrl":"https://doi.org/10.1002/cam4.70422","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Human nasopharyngeal carcinoma (NPC) cell lines are in vitro model systems that are widely available, easy to handle, and provide an unlimited supply of material. They also bypass ethical concerns associated with the use of primary human cells or tissue. However, many of these cell lines including 5-8F, 6-10B, CNE-1, CNE-2, HNE-1, HONE-1, SUNE1, SUNE2, and NPC-TW01 have been shown to be misidentified or cross-contaminated. While simple molecular genotyping techniques such as short tandem repeat profiling of human cell lines are available to confirm cell line identity, scientists often do not implement strategies to avoid misidentification. This has resulted in a large volume of publications containing incorrect information.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this paper, we have established a cell line karyogram that contains several marker chromosomes and a set of typical aberrations characteristic of NPC/HK1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusions</h3>\u0000 \u0000 <p>Combined with the typical multiloci short tandem repeat signature of NPC/HK1, the cytogenetic analysis provides an effective means to avoid unreliable experimental outcomes and scientific misinterpretation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70422","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111630","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":"Body Weight and Breast Cancer Treatment Experiences: Results From the Share Thoughts on a Breast Cancer Study","authors":"Sarah H. Nash,&nbsp;Elizabeth Verhage,&nbsp;Bradley D. McDowell,&nbsp;Joan Neuner,&nbsp;Elizabeth Chrischilles,&nbsp;Ingrid M. Lizarraga,&nbsp;Mary Schroeder","doi":"10.1002/cam4.70628","DOIUrl":"https://doi.org/10.1002/cam4.70628","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Differences in breast cancer recurrence and survival occur by body size; the role of treatment differences in these disparities has been underexplored. Our objective was to evaluate differences in treatments received, patient experiences of care, and treatment decision-making processes among breast cancer survivors by body size.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used data from the Share Thoughts on Breast Cancer study. Participants (<i>n</i> = 1198) completed a survey that included information on demographics, treatments received, quality of care, and decision-making. We used descriptive statistics to evaluate differences in survey response by BMI category, and multivariable-adjusted multinomial and logistic regression to examine associations of BMI with treatments received.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Those with higher BMI were more likely to be older, report fair/poor health, not have a college-level education, be non-white, not be insured, have an income under $50,000, be unemployed, and report a history of several chronic diseases. Although there were unadjusted associations, after adjustment, women with obesity were not significantly less likely to receive mastectomy [OR 0.79 (0.50, 1.26) and OR 0.66 (0.38, 1.16), for BMI 30–35 and 35+ kg/m² respectively] or contralateral prophylactic mastectomy [OR 0.92 (0.59, 1.44) and OR 0.80 (0.46, 1.39)] than those without obesity. Similarly, we found no association of BMI with reconstructive surgery [OR 0.97 (0.58, 1.60) and OR 0.58 (0.30, 1.11)] after adjustment. Women with obesity were less likely to report that their breast cancer care was excellent or very good (<i>p</i> = 0.026).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We observed no differences in breast cancer treatments received by BMI after adjustment for key covariates in this study sample. Further research is necessary to determine why quality of care may be perceived as lower among women with obesity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70628","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111631","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":"Lipid Profile, PCSK9, ANGPTL3 and Lipoprotein (a) Levels in Men Diagnosed With Localized High-Grade Prostate Cancer and Men At-Risk of Prostate Cancer","authors":"Ann-Charlotte Bergeron,&nbsp;Emilie Wong-Chong,&nbsp;France-Hélène Joncas,&nbsp;Chloé Castonguay,&nbsp;Frédéric Calon,&nbsp;Nabil G. Seidah,&nbsp;Jonatan Blais,&nbsp;Karine Robitaille,&nbsp;Alain Bergeron,&nbsp;Vincent Fradet,&nbsp;Anne Gangloff","doi":"10.1002/cam4.70587","DOIUrl":"10.1002/cam4.70587","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Some cancers have been found to require abundant supplies of lipids for their development. One example is prostate cancer (PCa). To date, lipid-modifying factors, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like 3 protein (ANGPTL3), and lipoprotein(a) or Lp(a), have not been reported in men with PCa. The present study aimed to verify whether plasma levels of these lipid-related proteins vary in men with PCa compared to at-risk but cancer-free men.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Plasma samples from 35 men with locally advanced PCa Gleason 8 and 9 versus 35 men at risk of PCa were selected as cases and controls. Blood samples were paired according to age and BMI. Apolipoprotein B100 (Apo B), Lp(a), and lipid profiles were measured on an analytical platform (Roche Cobas). PCSK9 and ANGPTL3 levels were determined by ELISA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No significant change in lipids and related factors levels was observed between men with localized PCa Gleason 8 or 9 and matched controls. A correlation between ANGPTL3 and HDL levels was only confirmed in controls (ρ = 0.54, <i>p</i> = 0.0009). PCSK9 was inversely associated with PSA levels in the entire cohort (ρ = −0.31, <i>p</i> &lt; 0.01), suggesting that factors influencing PCSK9 could also influence PSA levels. In controls only, PSA levels were correlated with LDL, Apo B, non-HDL, total cholesterol, and triglycerides (all ρ coefficients ≥ 0.35, all <i>p</i>-values &lt; 0.05). PCSK9 was correlated to LDL in PCa men, but the relationship was unexpectedly found to be inverse.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this observational study, lipid profiles, PCSK9, ANGPTL3, and Lp(a) levels did not change in men diagnosed with locally advanced Gleason 8 or 9 PCa compared to at-risk but cancer-free men. The present data suggest a complex interplay between PCSK9, PSA, and the lipid profile in localized PCa.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062423","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":"Lung Cancer Detection Using Bayesian Networks: A Retrospective Development and Validation Study on a Danish Population of High-Risk Individuals","authors":"Margrethe Bang Henriksen,&nbsp;Florian Van Daalen,&nbsp;Leonard Wee,&nbsp;Torben Frøstrup Hansen,&nbsp;Lars Henrik Jensen,&nbsp;Claus Lohman Brasen,&nbsp;Ole Hilberg,&nbsp;Inigo Bermejo","doi":"10.1002/cam4.70458","DOIUrl":"10.1002/cam4.70458","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lung cancer (LC) is the top cause of cancer deaths globally, prompting many countries to adopt LC screening programs. While screening typically relies on age and smoking intensity, more efficient risk models exist. We devised a Bayesian network (BN) for LC detection, testing its resilience with varying degrees of missing data and comparing it to a prior machine learning (ML) model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed data from 9940 patients referred for LC assessment in Southern Denmark from 2009 to 2018. Variables included age, sex, smoking, and lab results. Our experiments varied missing data (0%–30%), BN structure (expert-based vs. data-driven), and discretization method (standard vs. data-driven).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Across all missing data levels, area under the curve (AUC) remained steady, ranging from 0.737 to 0.757, compared to the ML model's AUC of 0.77. BN structure and discretization method had minimal impact on performance. BNs were well calibrated overall, with a net benefit in decision curve analysis when predicted risk exceeded 5%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>BN models showed resilience with up to 30% missing values. Moreover, these BNs exhibited similar performance, calibration, and clinical utility compared to the machine learning model developed using the same dataset. Considering their effectiveness in handling missing data, BNs emerge as a relevant method for the development of future lung cancer detection models.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062430","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":"Expression of Lymphoid Enhancer-Binding Factor 1 in Cancer-Associated Fibroblasts Mediates Tumor Growth and Transdifferentiation Toward Squamous Cell Carcinoma in Human Breast Cancer","authors":"Hiroya Okazaki,&nbsp;Yoshihiro Mezawa,&nbsp;Yang Shi,&nbsp;Mizuki Sakimoto,&nbsp;Zixu Wang,&nbsp;Akane Ishizuka,&nbsp;Kazunari Yamashita,&nbsp;Asahi Satoh,&nbsp;Yu Koyama,&nbsp;Yuki Fukumura,&nbsp;Kazunori Kajino,&nbsp;Atsushi Takano,&nbsp;Tomoyuki Yokose,&nbsp;Toshinari Yamashita,&nbsp;Yohei Miyagi,&nbsp;Yataro Daigo,&nbsp;Akira Katakura,&nbsp;Takehiro Yasukawa,&nbsp;Akira Orimo","doi":"10.1002/cam4.70627","DOIUrl":"10.1002/cam4.70627","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cancer-associated fibroblasts (CAFs) play a significant role in human breast cancer as a major stromal component. While their role in promoting cancer proliferation and malignancy through interaction with cancer cells in the tumor microenvironment is known, the exact mechanisms behind this interaction are not fully understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our study reveals that lymphoid enhancer-binding factor 1 (LEF1), a central transcription factor for Wnt/β-catenin signaling, is expressed in experimentally generated tumor-promoting CAFs (exp-CAFs) as well as in CAFs from breast cancer patients, particularly those with a poor prognosis. Notably, LEF1-expressing CAFs are prevalent in the stroma of squamous cell carcinoma (SCC), an aggressive metaplastic breast cancer subtype with a limited understanding of its development. To investigate the functional importance of LEF1 expression in CAFs, we depleted LEF1 in the exp-CAFs and subcutaneously implanted them along with breast ductal carcinoma MCF10DCIS.com cells into immunodeficient mice. Depleting LEF1 resulted in reduced xenograft tumor growth, accompanied by decreased cancer-cell proliferation and angiogenesis in the tumors. Additionally, we observed a significant reduction in the expression of SCC markers p40 (ΔNp63) and cytokeratin 5/6 in the xenograft tumors when LEF1 was depleted in the exp-CAFs. Furthermore, we identified 13 genes, none of which are established downstream genes of the Wnt/β-catenin pathway, that exhibit expression patterns similar to LFE1 in our cultured fibroblasts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In summary, our findings suggest that LEF1 expression contributes to the tumor-promoting abilities of breast CAFs and that LEF1-expressing CAFs may drive transdifferentiation toward SCC, possibly through a pathway independent of the canonical Wnt/β-catenin signaling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062486","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":"Haploidentical Stem Cell Transplantation With Dual Source of Cells and Post-Transplant Cyclophosphamide","authors":"Ana Marcela Rojas Fonseca-Hial,&nbsp;Katya Parisio,&nbsp;Jose Salvador Rodrigues de Oliveira","doi":"10.1002/cam4.70541","DOIUrl":"10.1002/cam4.70541","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dual sources of cells (DSC) with peripheral blood stem cell apheresis (PBSC) and surgical bone marrow (BM) for haploidentical hematopoietic cell transplantation (Hid-HCT) are used in China and some Asian countries. The experience of the Baltimore group for haploidentical transplant with post-transplant cyclophosphamide (PT-Cy) and reduced-intensity-conditioning (RIC) regimen used BM as a source of hematopoietic stem cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed 64 Hid-HCT with DSC and PT-Cy, RIC (<i>n</i> = 57), or myeloablative-conditioning (MAC) (<i>n</i> = 7), from two public health Brazilian centers, with a median follow-up of 23.3 months (6.7–45.4).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The 49 malignant patients were 27/46 (58.7%) beyond the first remission or with no complete response, and three patients did not complete disease status evaluation before transplant. Eight of 62 patients (12.9%) had grade 2 or more Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI), and two patients had no HCT-CI classified. Cytomegalovirus (CMV) viremia occurred in 26 of 57 (45.6%). The cumulative incidence of 100-day grade III-IV acute GVHD was 12.3% (7/57), with a 95% confidence interval (CI) of 3.8% and 20.8%, and 2-year moderate or severe chronic GVHD was 21.1% (11/52; 95% CI, 10.1%–32.3%). The 2-year relapses were 24.5% for malignant disease (12/49; 95% CI, 12.4%–36.5%). The 2-year overall survival (OS) probability was 54.7% (35/64; 95% CI, 42.5%–66.9%). Benign diseases achieve 2-year OS in 73.3% (11/15; 95% CI, 51%–95.7%) of the patients. The HCT-CI were significant in multivariate analyses for DFS (<i>p</i> = 0.002) and OS in uni- and multivariate analyses (both <i>p</i> &lt; 0.001). The number of CD34⁺ cells by apheresis collection was significant in multivariate analysis for DFS (<i>p</i> = 0.039).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Hid-HCT using PT-Cy, DSC, and RIC is a safe option for benign and malignant diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072946","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}