Cancer Medicine最新文献

{"title":"Predicting Grade and Patient Survival in Renal Cancer Using Machine Learning Analysis of Nucleolar Prominence","authors":"Elena Ivanova,&nbsp;Alexey Fayzullin,&nbsp;Victor Grinin,&nbsp;Dmitry Zhavoronkov,&nbsp;Dmitry Ermilov,&nbsp;Maxim Balyasin,&nbsp;Anna Timakova,&nbsp;Alesia Bakulina,&nbsp;Yusif Osmanov,&nbsp;Ekaterina Rudenko,&nbsp;Alexander Arutyunyan,&nbsp;Ruslan Parchiev,&nbsp;Nina Shved,&nbsp;Marina Astaeva,&nbsp;Aleksey Lychagin,&nbsp;Tatiana Demura,&nbsp;Peter Timashev","doi":"10.1002/cam4.71196","DOIUrl":"https://doi.org/10.1002/cam4.71196","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with clear cell renal cell carcinoma (ccRCC) often undergo organ resection, with treatment strategies based on recurrence risk. Current metastatic potential assessments rely on the WHO/ISUP grading system, which is subject to interobserver variability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We developed an artificial intelligence (AI) model to classify cells according to contemporary grading rules and evaluated the prognostic significance of tumor cell profiles, particularly focusing on cells with prominent nucleoli.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The model accurately distinguished low (G1/G2) and high (G3/G4) grades, achieving an area under the ROC curve of 0.79. Survival analysis identified four tissue patterns defined by total cell density and the proportion of cells with prominent nucleoli. The relative abundance of such cells had greater prognostic value than their mere presence, correlating with survival times ranging from 2.2 to over 6 years. Additionally, we confirmed that dystrophic changes and focal necrosis are linked to shorter survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that incorporating refined criteria into the WHO/ISUP system could enhance its prognostic accuracy in future revisions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 17","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71196","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021848","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":"Teleangiectatic Osteosarcoma Treated by Surgery and Chemotherapy: A Report of 223 Affected Patients From the Cooperative Osteosarcoma Study Group (COSS)","authors":"Stefan S. Bielack,&nbsp;Vanessa Mettmann,&nbsp;Daniel Baumhoer,&nbsp;Andreas Beilken,&nbsp;Claudia Blattmann,&nbsp;Godehard Friedel,&nbsp;Jendrik Hardes,&nbsp;Wolf Hassenpflug,&nbsp;Leo Kager,&nbsp;Matthias Kevric,&nbsp;Thekla von Kalle,&nbsp;Andreas Kulozik,&nbsp;Markus Metzler,&nbsp;Michaela Nathrath,&nbsp;Claudia Rossig,&nbsp;Benjamin Sorg,&nbsp;Mathias Werner,&nbsp;Stefanie Hecker-Nolting","doi":"10.1002/cam4.71211","DOIUrl":"https://doi.org/10.1002/cam4.71211","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Teleangiectatic osteosarcoma is a histologic subtype of osteosarcoma that can mimic aneurysmal bone cysts and has so far been incompletely characterized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients and Methods</h3>\u0000 \u0000 <p>We used the database of the Cooperative Osteosarcoma Study Group COSS (patient-registration 1980–2019) to better understand this rare histologic variant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>223 eligible patients were identified, 164 having reference pathology (median age 15.9 (3.7–69.7) years; male 134, female 89; tumor sites limb 208 (201 metaphyses, 66 pathologic fractures), trunk 13, head &amp; neck 2; 26 with primary metastases). Known tumor-predisposition syndromes were rare. Therapy included surgery in 215, radiotherapy in 10, and chemotherapy in all patients. Tumor response to preoperative treatment was good in 71% of 165 cases with available data. After a median follow-up of 7.1 (0.2–32.1) years for all patients and 10.5 (0.2–32.1) years for 152 survivors, 5-/10-year actuarial event-free and overall survival expectancies were 61%/57% and 73%/66%, respectively. Five unrelated malignancies occurred during this period. The presence of primary metastases, pathologic fracture, poor response to neoadjuvant chemotherapy, and not obtaining a complete macroscopic remission were associated with inferior outcomes for both event-free and overall survival (<i>p</i> &lt; 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>This large analysis proves teleangiectatic osteosarcoma to be a disease predominantly of the metaphyses of the young. While detected only rarely, the true incidence of genetic tumor predispositions would require prospective assessments. Behaving like other osteosarcoma subtypes in many other ways, this variant may show greater chemosensitivity and hence somewhat better outcomes than other subtypes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 17","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71211","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012982","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":"BMI-dependent prognostic role of EEF1G in breast cancer: A 15-year follow-up of the Guangzhou Breast Cancer Cohort Study","authors":"Na Li,&nbsp;Chengkun Xiao,&nbsp;Shushu Han,&nbsp;Minjie Lu,&nbsp;Qianxin Chen,&nbsp;Yuanzhong Yang,&nbsp;Luying Tang,&nbsp;Zefang Ren,&nbsp;Lin Xu","doi":"10.1002/cam4.70227","DOIUrl":"https://doi.org/10.1002/cam4.70227","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Eukaryotic elongation factor 1 gamma (EEF1G) has emerged as a potential prognostic marker in various malignancies. Yet, its association with breast cancer (BC) prognosis, particularly in the context of body mass index (BMI) status, remains unexplored. Therefore, we investigated the prognostic value and role of EEF1G in BC across different BMI categories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>EEF1G expression was assessed through immunohistochemistry in tissue microarrays on 1011 patients with primary invasive BC. Prognostic effects were analyzed using the Cox proportional hazards regression. GSE78958 dataset downloaded from the Gene Expression Omnibus (GEO) database was used to validate our findings. Gene Set Enrichment Analysis (GSEA) was performed using R packages, and protein–protein interaction (PPI) networks were generated using the STRING database and Cytoscape software.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Elevated EEF1G expression was associated with a better prognosis in patients with BMI ≤ 24 kg/m² (hazard ratio (HR) for overall mortality = 0.67, 95% confidence interval (CI): 0.43–1.03; HR for progression = 0.60, 95% CI: 0.42–0.86). In contrast, for patients with BMI &gt; 24 kg/m², it appeared to be associated with poorer outcomes (HR for overall mortality = 1.74, 95% CI: 0.96–3.17; HR for progression = 1.63, 95% CI: 1.00–2.66). In patients with BMI &gt; 24 kg/m², EEF1G was associated with specific metabolic and oncogenic pathways, which were not statistically significant in patients with BMI ≤ 24 kg/m². The top interacting genes with <i>EEF1G</i> differed between the BMI categories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study showed EEF1G expression was inversely associated with BC prognosis in different BMI categories, indicating its potential as a prognostic marker and therapeutic target in BC. The differential effects underscore the need for personalized approaches in BC management and research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 17","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70227","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021885","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":"Cellular Senescence and Immunosenescence in Melanoma: Insights From the Tumor Microenvironment","authors":"Lihua Xiong,&nbsp;Jian Cheng","doi":"10.1002/cam4.71223","DOIUrl":"https://doi.org/10.1002/cam4.71223","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Melanoma is one of the most immunogenic malignancies, yet resistance to immune checkpoint inhibitors (ICIs) remains a major obstacle to durable therapeutic success. Emerging evidence indicates that aging-related processes, including cellular senescence and immunosenescence, can reshape the tumor microenvironment (TME) to favor immune evasion and disease progression. Senescent melanoma and stromal cells secrete a senescence-associated secretory phenotype (SASP) that alters immune cell recruitment and function, while immunosenescence leads to diminished cytotoxic responses and the accumulation of dysfunctional or suppressive immune subsets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This review explores the interplay between cellular senescence and immunosenescence in melanoma, highlighting their contributions to tumor progression and immunotherapy resistance, and discusses potential strategies to therapeutically target senescence-related pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic review of studies published between 2000 and 2024 was performed using PubMed, Web of Science, and Scopus. Literature included mechanistic investigations of senescence in melanoma, analyses of immunosenescence in cancer patients, and preclinical or translational studies targeting senescence-related pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusions</h3>\u0000 \u0000 <p>Senescent tumor and stromal cells drive a pro-inflammatory and immunosuppressive TME through SASP, while aging immune cells exhibit impaired antigen presentation, reduced cytotoxicity, and increased suppressive subsets. These dual processes form a self-reinforcing cycle of chronic inflammation and immune dysfunction, ultimately undermining the efficacy of ICIs. Targeting senescence, through senolytics, senostatics, or SASP modulators, has shown promise in preclinical models and may restore immune competence in melanoma. However, clinical translation requires further investigation to validate safety and efficacy. Addressing both cellular and immune senescence represents a novel and promising direction to overcome therapeutic resistance and improve melanoma outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 17","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021886","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":"Exploring the Functional Role of Programmed Death-Ligand 1 (PD-L1) in the Castration-Resistant Prostate Cancer Using Transcriptomic Sequencing Analysis","authors":"Lin Zhong,&nbsp;Pengxin Zhang,&nbsp;Jialin Ji,&nbsp;Jun Mao,&nbsp;Lianhong Li","doi":"10.1002/cam4.71225","DOIUrl":"https://doi.org/10.1002/cam4.71225","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Prostate cancer is one of the principal malignancies threatening human health, and the development of castration resistance often constitutes a major cause of treatment failure in its management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To elucidate the potential association between programmed death-ligand 1 (PD-L1) and castration resistance in prostate cancer, we analyzed the expression levels of PD-L1 in both primary prostate cancer tissues and castration-resistant prostate cancer (CRPC) specimens as well as in corresponding cell lines by using western blots and immunohistochemistry. Then, we explored the specific mechanisms through transcriptomic sequencing technology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings revealed that, compared to adjacent non-cancerous tissue, PD-L1 expression was unexpectedly lower in primary prostate cancer but notably elevated in CRPC tissues and cells. In CRPC cell lines where PD-L1 was knocked down, a significant suppression of proliferation, invasion, and migration capabilities was observed. By employing next-generation sequencing technology, we investigated the impact of PD-L1 knockdown on intracellular signaling pathways in castration-resistant cells. The results demonstrated that PD-L1 knockdown led to alterations in gene expression within several signaling pathways, including those involved in cell surface interactions, regulation of natural killer cell activity, and sodium channel regulatory activity. We further elucidated through experimentation that PD-L1 contributes to tumor progression in CRPC by modulating the expression of SCUBE1. More intriguingly, PD-L1 knockdown also appeared to induce changes at the level of alternative splicing in multiple genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>PD-L1 is upregulated in CRPC and can modulate the expression of multiple tumor-associated genes in CRPC cells. Finally, we found that PD-L1 contributes to tumor progression in CRPC by modulating the expression of SCUBE1. This study provides a theoretical basis for understanding the intracellular signaling mediated by PD-L1 and offers valuable insights into the mechanisms underlying castration resistance in prostate cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 17","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71225","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjuvant Chemotherapy for Patients With Chronic Kidney Disease: A Study on Treatment Adoption and Associated Factors","authors":"Taisuke Ishii,&nbsp;Tomone Watanabe,&nbsp;Yuichi Ichinose,&nbsp;Hiroyuki Mano,&nbsp;Takahiro Higashi","doi":"10.1002/cam4.71237","DOIUrl":"https://doi.org/10.1002/cam4.71237","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Patients with chronic kidney disease (CKD) face unique challenges in cancer treatment, including the need for chemotherapy dose adjustments and avoiding nephrotoxic agents, often leading to less aggressive treatment. However, little is known about the real-world administration of adjuvant chemotherapy for patients with CKD. In this study, we aimed to investigate the prevalence of adjuvant chemotherapy in patients with CKD and to explore factors influencing chemotherapy use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed data from the Diagnosis Procedure Combination survey and hospital-based cancer registry in Japan. Adult patients diagnosed with colon, gastric, breast, or non-small-cell lung cancer who underwent curative surgery from January 2016 to December 2019 were included. CKD was identified based on International Classification of Diseases, 10th revision codes, and CKD-related medication prescriptions. The primary outcome was the proportion of patients receiving adjuvant chemotherapy, and secondary outcomes were regimen details.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 109,875 patients were included in the study, 4.5% (4953) of whom had CKD. Patients with CKD were older and had a higher prevalence of comorbidities. A smaller proportion of patients with CKD received adjuvant chemotherapy (41.7% vs. 64.5%, <i>p</i> &lt; 0.001). CKD was independently associated with lower odds of receiving adjuvant chemotherapy (odds ratio: 0.51, 95% confidence interval: 0.48–0.55). Patients with CKD were also less likely to receive standard chemotherapy regimens or those requiring dose adjustments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patients with CKD received adjuvant chemotherapy less frequently, likely owing to concerns about kidney toxicity and dose adjustments. Individualized treatment approaches are needed to optimize outcomes for this population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 17","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012740","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":"Outcomes of Novel Hormonal Therapies in Men With Advanced Prostate Cancer by Treating Specialist","authors":"Kassem S. Faraj,&nbsp;Mary Oerline,&nbsp;Samuel Kaufman,&nbsp;Avinash Maganty,&nbsp;Megan E. V. Caram,&nbsp;Vahakn B. Shahinian,&nbsp;Brent K. Hollenbeck","doi":"10.1002/cam4.71219","DOIUrl":"https://doi.org/10.1002/cam4.71219","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>In the past decade, the management of advanced prostate cancer has shifted to novel hormonal therapies. As a result, urologists have increased their involvement in the management of advanced prostate cancer. These therapies require close monitoring due to the possibility of adverse cardiometabolic events. We assessed outcomes among men diagnosed with advanced prostate cancer started on novel hormonal therapy by a urologist compared to those by a medical oncologist.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a retrospective cohort study of Medicare beneficiaries with advanced prostate cancer treated with a novel hormonal therapy between 2012 and 2019. The primary outcome was an adverse event comprised of a hospital visit for a cardiometabolic event within 6 months of starting a novel hormonal therapy. Secondary outcomes included monthly out-of-pocket costs and treatment adherence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were 1212 (23%) and 4124 (77%) patients who were prescribed a novel hormonal therapy for the first time by a urologist and medical oncologist, respectively. No difference in the composite adverse event measure was observed in those managed by urologists or medical oncologists (4.2% vs. 4.7%, respectively, <i>p</i> = 0.49). Out-of-pocket costs, in men without low-income subsidies, did not vary by specialty ($772 vs. $790, <i>p</i> = 0.58). Adherence to treatment did not vary in men managed by urologists or medical oncologists (75% vs. 74%, respectively, <i>p</i> = 0.64).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The specialty of the physician prescribing a novel hormonal therapy was not associated with the risk of a cardiometabolic adverse event. Further, management by a urologist did not adversely affect costs to patients or adherence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 17","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71219","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012981","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":"Comparative Effectiveness of Direct Oral Anticoagulants and Warfarin on Venous Thromboembolism in Cancer Patients","authors":"Hye-In Jung,&nbsp;Claudia Geue,&nbsp;Giorgio Ciminata,&nbsp;Eui-Kyung Lee","doi":"10.1002/cam4.71209","DOIUrl":"https://doi.org/10.1002/cam4.71209","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Venous thromboembolism (VTE) is a leading cause of mortality in cancer patients, and a substantial number of patients are being treated with oral anticoagulants. We aim to assess the comparative effectiveness of direct oral anticoagulants (DOACs) compared to warfarin for VTE treatment in cancer patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this retrospective cohort study, we included 2,367 cancer patients who are new users of oral anticoagulants (OACs) for VTE treatment from 2009 to 2021 in NHS Scotland. Patients were grouped by OAC type, DOACs or warfarin. To adjust for confounding, inverse probability treatment weighting was applied. Outcomes included mortality, VTE recurrence, and major bleeding. We calculated Hazard Ratio (HR) using Cox regression and sub-distribution HR (sHR) using a competing risk framework (Fine and Gray method) for VTE recurrence and major bleeding. Subgroup analyses were conducted for individual DOACs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients on DOACs had lower risks of VTE recurrence (sHR 0.73 95% CI 0.59–0.90) and major bleeding (sHR 0.68, 95% CI 0.53–0.88) compared to patients on warfarin. Patients on rivaroxaban (HR 1.21, 95% CI 1.04–1.39) and edoxaban (HR 1.59, 95% CI 1.15–2.22) had a significantly higher risk of mortality, while a comparable risk of mortality was observed (HR 0.91, 95% CI 0.76–1.08) for patients on apixaban compared to patients on warfarin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides insight into the effectiveness of DOACs compared to warfarin for VTE in cancer patients. Patients on DOACs had lower risks of VTE recurrence and major bleeding. We suggest healthcare professionals consider the potential benefits of individual DOACs when making treatment decisions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 17","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71209","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012983","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":"Interpretable Machine Learning for Predicting Neoadjuvant Chemotherapy Response in Breast Cancer Using the Baseline Clinical and Pathological Characteristics","authors":"Shan Fang,&nbsp;Jun Zhang,&nbsp;Chengyan Han,&nbsp;Mingxiang Kong,&nbsp;Haibo Zhang,&nbsp;Miaochun Zhong,&nbsp;Wuzhen Chen,&nbsp;Hongjun Yuan,&nbsp;Wenjie Xia,&nbsp;Wei Zhang","doi":"10.1002/cam4.71221","DOIUrl":"https://doi.org/10.1002/cam4.71221","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The pathological response to neoadjuvant chemotherapy (NAC) has become a vital prognostic indicator for patients with breast cancer (BC). The newly generated models depended on rather basic imaging and pathology characteristics and did not sufficiently elucidate the importance of the incorporated data. The purpose of this study is to establish and authenticate a machine learning model for predicting the pathological complete response to NAC using baseline clinical and pathological features in BC patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were collected from hospitalized BC patients treated with NAC at Zhejiang Provincial People's Hospital between January 2014 and August 2023. The dataset was randomly split, with 70% allocated for model training and 30% for validation. LASSO regression was used to select predictive features. Six ML models—XGBoost, LightGBM, CatBoost, logistic regression, random forest (RF), and support vector machine (SVM)—were developed, with performance assessed using the area under the curve (AUC) and accuracy, precision, recall, F1 score, and Brier score. Clinical benefits were evaluated using decision curve analysis (DCA), and SHapley Additive exPlanation (SHAP) was applied to interpret the features of the optimal ML model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 303 <span>bc</span> patients treated with NAC were included, with a pCR rate of 29.37% (89/303). Twelve features, such as age, menopausal status, PR, HER2 status, Ki-67 expression, stromal tumor-infiltrating lymphocytes (sTILs) et al., were selected for model construction. Among the six models, the CatBoost model demonstrated the best predictive performance, achieving an AUC of 0.853 after Bayesian hyperparameter tuning. SHAP analysis ranked sTILs as the most critical predictive feature. In fivefold cross-validation, the CatBoost model incorporating sTILs achieved an average AUC of 0.83.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The ML-based pCR prediction model enables more accurate pCR prediction for BC patients at baseline, aiding in optimizing treatment strategies. Additionally, the interpretable SHAP framework enhances model transparency, fostering clinical trust, and understanding among doctors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 17","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71221","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012470","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":"Treatment and Survival for Unresectable Pancreatic Adenocarcinoma in Queensland, Australia, 2018–2022","authors":"Danny R. Youlden,&nbsp;Bryan A. Chan,&nbsp;Jon Clark,&nbsp;Victoria K. Donoghue,&nbsp;Michael J. Allen","doi":"10.1002/cam4.71226","DOIUrl":"https://doi.org/10.1002/cam4.71226","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The three main chemotherapy regimens for people with unresectable pancreatic cancer include modified FOLFIRINOX (comprising oxaliplatin, irinotecan and fluorouracil, denoted mFFX), gemcitabine with nab-paclitaxel (GnP), and single-agent gemcitabine (GEM). We explored characteristics associated with the type of chemotherapy and variations in survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Records for people with unresected pancreatic adenocarcinoma between 2018 and 2022 treated with first-line mFFX, GnP or GEM were extracted from the population-based Queensland Oncology Repository. Multivariable Poisson models were fitted to determine factors associated with each type of chemotherapy, expressed as relative likelihoods (RLs). Variations in three-year observed survival were assessed using flexible parametric modelling and reported in terms of adjusted excess mortality hazard ratios (HRs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 766 people in the study cohort, 59% were treated with GnP, 27% with mFFX, and 15% with GEM. After adjustment, treatment with mFFX was far more likely in selected private facilities compared to public hospitals (RL = 2.33, 95% CI 1.84–2.96), whereas the GEM regimen was used more often for those from outer regional/remote areas (RL = 2.20 compared to people living in major cities, 95% CI 1.45–3.34; <i>p</i> &lt; 0.001). Three-year survival was very poor at just 5% (95% CI 3%–7%). Nonetheless, adjusted mortality was higher for GnP (HR = 1.30, 95% CI 1.07–1.59) and GEM (HR = 1.53, 95% CI 1.17–2.01) compared to mFFX.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Apart from clinical indications, there should be equity in the treatment received for unresectable pancreatic cancer. Our results suggest, however, that where a person lives and the type of facility at which they are treated may influence their chemotherapy regimen.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"14 17","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.71226","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012317","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}