Therapeutic Advances in Medical Oncology最新文献

{"title":"Impact of asthma and/or chronic obstructive pulmonary disease on the survival of patients with lung adenocarcinoma.","authors":"Li-Han Hsu, Yi-Hsuan Lin, An-Chen Feng, Nei-Min Chu, Shu-Huei Kao","doi":"10.1177/17588359251355412","DOIUrl":"10.1177/17588359251355412","url":null,"abstract":"<p><strong>Background: </strong>Chronic airway inflammation in asthma and/or chronic obstructive pulmonary disease (COPD) is presumed to be protumorigenic. The tumor inhibitory effect of inhaled corticosteroids (ICSs) used to reduce airway inflammation in patients with asthma and COPD remains unclear.</p><p><strong>Objectives: </strong>This study aimed to evaluate the impact of coexisting asthma and/or COPD on the survival of patients with lung adenocarcinoma. The effects of ICS treatment were also assessed.</p><p><strong>Design: </strong>This retrospective, real-world cohort study was conducted at a cancer center.</p><p><strong>Methods: </strong>The overall survival of a cohort of 1524 consecutive patients with lung adenocarcinoma who were enrolled between January 2011 and December 2019 and followed up until December 2022 was analyzed, followed by subgroup comparisons.</p><p><strong>Results: </strong>A total of 283 patients had coexisting asthma and/or COPD. Among them, 212 had used ICSs. ICS users were predominantly women, older, and had more advanced-stage disease; moreover, there were fewer tobacco smokers, fewer comorbidities, and relatively severe obstructive impairments than non-ICS users. When restricted to stage 0-II diseases, patients with coexisting asthma and/or COPD had a lower 5-year overall survival rate (77% vs 90%, <i>p</i> < 0.001), with a hazard ratio of 1.8, in contrast to no difference among patients with stage III-IV disease. ICS users had a lower 5-year overall survival rate in both subgroups, although the difference was not statistically significant.</p><p><strong>Conclusion: </strong>The impact of cancer on prognosis may overwhelm the effects of asthma and/or COPD in patients with advanced-stage lung adenocarcinoma. The evaluation of the effects of ICS treatment appears to be confounded by intent and compliance, which can introduce bias in the opposite direction. However, investigating the treatment effects on asthma and/or COPD control would be beneficial. A systematic prospective study is required to define the role of the ICS.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251355412"},"PeriodicalIF":4.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627107","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":"Understanding and overcoming CDK4/6 inhibitor resistance in HR+/HER2- metastatic breast cancer: clinical and molecular perspectives.","authors":"Jessé Lopes da Silva, Leandro Jonata de Carvalho Oliveira, Cristiano Augusto Andrade de Resende, Tomas Reinert, Lucas Zanetti de Albuquerque, Luís Felipe Leite da Silva, Max Senna Mano","doi":"10.1177/17588359251353623","DOIUrl":"10.1177/17588359251353623","url":null,"abstract":"<p><p>This narrative review explores the mechanisms underlying resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in hormone receptor (HR)-positive metastatic breast cancer (MBC), a critical challenge in contemporary oncology. Despite the proven efficacy of CDK4/6i in improving clinical outcomes, both intrinsic and acquired resistance remain substantial challenges. We discuss clinical data that underscore pivotal molecular alterations associated with resistance, including mutations in the <i>Retinoblastoma gene</i> (<i>RB1</i>), germline variants, aberrations in the <i>PIK3CA</i> gene that activate the phosphatidylinositol 3-kinase/protein kinase B (AKT)/mammalian target of rapamycin signaling cascade, and modifications in fibroblast growth factor receptor signaling. Additional resistance mechanisms-such as the loss of the <i>FAT1</i> tumor suppressor gene and the dysregulation of cell cycle regulators like <i>cyclin E</i> and <i>CDK2</i>-are also explored. The role of circulating tumor DNA analysis in tracking genomic changes during therapy is also considered. Furthermore, the review assesses emerging therapeutic strategies, particularly combination therapies that target alternative pathways to counteract resistance mechanisms. By synthesizing current evidence and providing actionable insights, this review aims to enhance our understanding of endocrine resistance mechanisms among clinical oncologists and gives them some future perspectives to expand strategies to overcome this challenge.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251353623"},"PeriodicalIF":4.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627109","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":"Clinicopathological and molecular significance of HER2-low expression in Asian women with triple-negative breast cancer.","authors":"Cuiyan Yang, Haoyu Wang, Yiwei Tong, Zheng Wang, Xi Sun, Anqi Li, Yujie Lu, Mengyuan Han, Siji Zhu, Lei Dong, Kunwei Shen, Xiaosong Chen","doi":"10.1177/17588359251353083","DOIUrl":"10.1177/17588359251353083","url":null,"abstract":"<p><strong>Background: </strong>Heterogeneity of human epidermal growth factor receptor 2 (HER2) expression exists in triple-negative breast cancer (TNBC). The evolution of the HER2 testing algorithm has led to the new classification of the HER2-low category, with unclear clinicopathological and molecular features in Asian women with HER2-low TNBC.</p><p><strong>Objectives: </strong>This study aimed to assess the clinicopathological and molecular characteristics of HER2-low TNBC in Asian women.</p><p><strong>Design: </strong>Our study prospectively included 3376 patients with TNBC diagnosed from 2009 to 2021 in the Shanghai Jiao Tong University Breast Cancer Database (a multicenter dataset), and 92 patients from The Cancer Genome Atlas (TCGA) cohort were enrolled.</p><p><strong>Methods: </strong>Two different independent TNBC cohorts were included, a multicenter cohort (Whole cohort, <i>n</i> = 3376) and the TCGA cohort (<i>n</i> = 92). Genomic profiling covering 32 mutations for Homologous Recombination Repair and other cancer predisposition genes was obtained. Clinicopathological features, genomic status of the above genes, treatment response, and disease prognosis were compared between HER2-low and HER2-zero TNBC patients.</p><p><strong>Results: </strong>In Asian females, 1611 (47.72%) TNBC patients were HER2-low. HER2-low was associated with a higher percentage of postmenopausal status (odds ratio (OR) = 1.64, <i>p</i> < 0.001), lymph node positivity (OR = 1.14, <i>p</i> = 0.003), and invasive ductal carcinoma histology (OR = 1.21, <i>p</i> = 0.012). HER2-low group had less <i>BRCA1</i> mutation (7.02% vs 13.76%, <i>p</i> = 0.038) but was associated with a higher rate of <i>PIK3CA</i> mutation (28.07% vs 12.17%, <i>p</i> < 0.001) compared with HER2-zero TNBC. No significant difference in breast pathologic complete response rate, breast cancer-free interval, or overall survival was observed between HER2-low and HER2-zero TNBC. In the TCGA cohort, lipid metabolism genes were upregulated in the HER2-low TNBC, enriched in alpha-linolenic acid metabolism (normalized enrichment score = 1.51, <i>p</i> = 0.019).</p><p><strong>Conclusion: </strong>Our results show that HER2-low TNBC had specific clinicopathological, genomic profiling, and biological features compared with HER2-zero TNBC in Asian women, but without significant differences in treatment response and prognosis, warranting exploring better treatment strategies to improve disease outcomes.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251353083"},"PeriodicalIF":4.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627147","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":"Efficacy of zanubrutinib versus acalabrutinib for relapsed or refractory chronic lymphocytic leukemia (R/R CLL): a matching-adjusted indirect comparison (MAIC).","authors":"Mazyar Shadman, Jennifer R Brown, Rhys Williams, Leyla Mohseninejad, Keri Yang, Pal Rakonczai, Nicole Lamanna, Sheng Xu, Aileen Cleary Cohen, Susan M O'Brien, Alessandra Tedeschi, Constantine S Tam","doi":"10.1177/17588359251340554","DOIUrl":"10.1177/17588359251340554","url":null,"abstract":"<p><strong>Background: </strong>There are no head-to-head studies comparing the efficacy of the Bruton tyrosine kinase inhibitors, zanubrutinib and acalabrutinib, in relapsed or refractory chronic lymphocytic leukemia (R/R CLL).</p><p><strong>Objective: </strong>To compare the relative efficacy of zanubrutinib and acalabrutinib in R/R CLL using indirect treatment comparison.</p><p><strong>Design: </strong>An unanchored matching-adjusted indirect comparison (MAIC) was performed.</p><p><strong>Methods: </strong>Individual patient-level data from ALPINE (zanubrutinib) were reweighted using prognostic/effect-modifying variables to match aggregate data from ASCEND (acalabrutinib). MAIC outcomes included investigator-assessed progression-free survival (PFS-INV), overall survival (OS), and complete response (CR).</p><p><strong>Results: </strong>Post-matching, PFS-INV was improved significantly for zanubrutinib versus acalabrutinib (hazard ratio (HR) = 0.68 (95% confidence interval (CI): 0.46-0.99); <i>p</i> = 0.0448) and OS showed a trend toward improvement for zanubrutinib (HR = 0.60; 95% CI: 0.35-1.02, <i>p</i> = 0.0575). CR was significantly higher for zanubrutinib versus acalabrutinib (odds ratio = 2.90 (95% CI: 1.13-7.43); <i>p</i> <i>=</i> 0.0270).</p><p><strong>Conclusion: </strong>Zanubrutinib was associated with a significant PFS-INV and CR advantage over acalabrutinib, with a trend toward improvement in OS.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251340554"},"PeriodicalIF":4.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627105","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 utility of ctDNA testing in high-risk breast cancer patients in a community setting: case series.","authors":"Kasen Wong, Alyssa Kameoka, Jami Aya Fukui","doi":"10.1177/17588359251351121","DOIUrl":"10.1177/17588359251351121","url":null,"abstract":"<p><p>Despite initial treatment, breast cancer recurrence affects approximately 30% of patients. Currently, there exists no standardized approach to detect recurrence before clinical or radiologic signs manifest. Circulating tumor DNA (ctDNA) is a minimally invasive blood test that offers potential to monitor molecular disease and individualize care. This study explores the utility of ctDNA in recurrence monitoring and clinical decision-making for high-risk breast cancer cases within a community setting. Seventy-two patients with high-risk breast cancer features-defined as stage III disease, triple-negative or HR-/HER2+ following neoadjuvant treatment, metastatic breast cancer without evidence of disease, bilateral breast cancer history, high-risk genetics (BRCA1/BRCA2 mutations), <40 years old at diagnosis, or history of breast cancer recurrence-were offered tumor-informed ctDNA assays at 3- to 6-month intervals. Analysis was conducted on 67 cases with a mean diagnostic age of 52.69 at diagnosis. The cohort was ethnically diverse, including White (<i>n</i> = 21, 31.82%), Japanese (<i>n</i> = 15, 22.73%), Native Hawaiian (<i>n</i> = 11, 16.67%), and Filipino (<i>n</i> = 7, 10.61%) patients. Seven (10.45%) tests were positive: six predicted recurrence despite four with initially negative radiological findings, and one prompted treatment resumption following prior non-adherence. However, one negative result was false and later showed a contralateral breast recurrence, and another negative test coincided with a new primary cholangiocarcinoma. In two cases, ctDNA negativity was utilized to monitor treatment response in metastatic disease and inform therapeutic adjustments. In real-world settings, ctDNA served as a valuable tool for earlier recurrence prediction, expediting radiological confirmation, and influencing treatment. Nevertheless, false results carry the risk of hindering effective care and inducing considerable patient anxiety. Future large-scale studies are warranted in high-risk breast cancer populations to evaluate ctDNA's impact on patient survival outcomes, treatment monitoring, and patients' emotional experiences.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251351121"},"PeriodicalIF":4.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627106","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":"Depression and anxiety in patients with breast cancer receiving radiotherapy: a longitudinal study.","authors":"Shi-Jia Wang, Xin Feng, Wei Zhang, Guang-Yi Sun, Hui Fang, Hao Jing, Yu Tang, Tao Li, Shu-Nan Qi, Yong-Wen Song, Wen-Wen Zhang, Ning-Ning Lu, Yuan Tang, Yue-Ping Liu, Bo Chen, Xin Liu, Ye-Xiong Li, Yi-Rui Zhai, Shu-Lian Wang","doi":"10.1177/17588359251345930","DOIUrl":"10.1177/17588359251345930","url":null,"abstract":"<p><strong>Background: </strong>Depression and anxiety are common among patients with breast cancer, but prospective studies of depression and anxiety after radiotherapy (RT) among these patients remain scarce.</p><p><strong>Objective: </strong>To evaluate the prevalence of and changes in depression and anxiety among patients with breast cancer from the first day of RT (T0) to 6 months post-RT, and to identify risk factors associated with depression and anxiety and higher levels of them over time.</p><p><strong>Design: </strong>This observational study used a prospective, longitudinal design.</p><p><strong>Methods: </strong>This study was conducted in China between August 2022 and August 2023. Depression and anxiety were measured, respectively, by Patient Health Questionnaire and the Generalized Anxiety Disorder Scale, from T0 to 6 months post-RT. Univariate and multivariate logistic regressions were performed to explore risk factors for baseline depression and anxiety. Generalized Estimating Equations were performed to evaluate changes in depression and anxiety and risk factors for higher levels of them over time.</p><p><strong>Results: </strong>A total of 504 patients completed baseline questionnaires (response rate: 90.9%). The prevalence of depression and anxiety decreased significantly over time, from 37.3% and 26.0% at T0, to 28.4% and 20.3% at 6 months post-RT, respectively. Having a family history of cancer and receiving anti-HER2-targeted therapy were independently associated with depression at T0, and premenopausal status, poor family income, and self-reported menopausal symptoms were independently associated with both depression and anxiety at T0. Receiving anti-HER2-targeted therapy, having a lower personal income, and living in rural areas were associated with higher depression levels over time, whereas poor family income and self-reported menopausal symptoms were associated with higher anxiety levels over time.</p><p><strong>Conclusion: </strong>Depression and anxiety levels were high among patients with breast cancer receiving RT and decreased over time from pre-RT to 6 months post-RT. Routine screening is necessary, especially for high-risk patients.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251345930"},"PeriodicalIF":4.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627148","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":"Unveiling the best immune checkpoint inhibitor-based therapy for metastatic renal cell carcinoma in the first-line setting: an updated systematic review and Bayesian network analysis.","authors":"Junpeng Wang, Xin Li, Mengjun Li, Qingyuan Liu, Zixuan Xie, Xiaotian Si, Lei Yang, Zhifeng Wang, Degang Ding","doi":"10.1177/17588359251353259","DOIUrl":"10.1177/17588359251353259","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitor (ICI)-based combination therapies have been recommended as first-line options for metastatic renal cell carcinoma (mRCC); however, no head-to-head randomized controlled trials (RCTs) have compared all existing ICI-based therapies.</p><p><strong>Objective: </strong>We aimed to analyze the updated data to compare the efficacy of all available ICI-based options for mRCC.</p><p><strong>Design: </strong>A systematic review and Bayesian network analysis.</p><p><strong>Data sources and methods: </strong>A systematic literature search was undertaken up to September 15, 2024, and subsequent analysis was performed using a Bayesian fixed-effect model.</p><p><strong>Results: </strong>This study included 30 RCTs involving 14,959 patients. The results revealed that nivolumab plus cabozantinib (hazard ratio (HR): 0.77; 95% credible interval (CrI): 0.63-0.93), pembrolizumab plus lenvatinib (HR: 0.79; 95% CrI: 0.64-0.99), toripalimab plus axitinib (HR: 0.62; 95% CrI: 0.42-0.97), nivolumab plus ipilimumab (HR: 0.72; 95% CrI: 0.62-0.84), pembrolizumab plus axitinib (HR: 0.84; 95% CrI: 0.71-0.98), and avelumab plus axitinib (HR: 0.79; 95% CrI: 0.64-0.98) were significantly more effective than sunitinib for overall survival (OS). Most ICI-based combination treatments resulted in fewer or similar high-grade adverse events compared to sunitinib, except for pembrolizumab plus lenvatinib. For favorable-risk patients, ICI-based combination therapies were not more effective than sunitinib in OS, while six ICI-based combination therapies were associated with significantly improved OS compared to sunitinib for intermediate-risk or poor-risk patients.</p><p><strong>Conclusion: </strong>Our findings demonstrated that combination therapies including nivolumab plus cabozantinib, pembrolizumab plus lenvatinib, toripalimab plus axitinib, nivolumab plus ipilimumab, pembrolizumab plus axitinib, and avelumab plus axitinib significantly improved OS versus sunitinib. For subgroup analysis, ICI-based combination therapies exhibited significant advantages over sunitinib for intermediate-risk or poor-risk patients, while such advantages were diminished in treating favorable-risk patients.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251353259"},"PeriodicalIF":4.3,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592433","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":"Immunotherapy in metastatic prostate cancer.","authors":"Liam Dwyer, Claudia Leslie, Rhiannon Mellor, Tahlia Scheinberg, Renea A Taylor, Lisa G Horvath","doi":"10.1177/17588359251347857","DOIUrl":"10.1177/17588359251347857","url":null,"abstract":"<p><p>Over the last 15 years, immunotherapy has revolutionised treatment paradigms and improved outcomes in a range of malignancies. Despite these advances, the role of immunotherapy in standard prostate cancer (PCa) management is limited, and Sipuleucel-T is the only approved immunotherapeutic agent. This article reviews the role of checkpoint inhibitors (ICIs), T-cell engagers (TCEs) and chimeric antigen receptor (CAR)-T cells in PCa treatment. Phase II/III trials of ICIs as monotherapy or combination treatment have been negative to date. Early phase data for TCE are promising, but the feasibility of adoption of TCEs into the clinic will depend on overcoming neutralising anti-drug antibodies and limiting toxicities. CAR-T cells have demonstrated feasibility and acceptable safety profiles in early phase clinical trials, and it is hoped that the ongoing development of later-generation constructs and therapeutic combinations will enhance outcomes.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251347857"},"PeriodicalIF":4.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576328","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 machine learning-based prognostic stratification of locoregional interventional therapies for patients with colorectal cancer liver metastases: a real-world study.","authors":"Jing Wang, Kai Wang, Kangjie Wang, Baogen Zhang, Siyu Zhu, Xuyang Zhang, Li Wang, Yingying Tong, Aiwei Feng, Haibin Zhu, Ting Xu, Xu Zhu, Dong Yan","doi":"10.1177/17588359251353084","DOIUrl":"10.1177/17588359251353084","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer liver metastases (CRLM) represent a major cause of mortality in advanced colorectal cancer, with intra-arterial interventional therapy (IAIT) playing an increasingly important role in multidisciplinary management. This study aims to develop a machine learning (ML)-based prognostic model to predict survival outcomes in unresectable colorectal cancer liver metastases (uCRLM) patients undergoing IAIT treatment, enabling improved risk assessment.</p><p><strong>Design: </strong>A retrospective study.</p><p><strong>Objectives: </strong>This study aims to explore the effect of IAIT on the survival of patients with uCRLM.</p><p><strong>Methods: </strong>Retrospective data were obtained from patients with CRLM who visited Luhe Hospital and Peking University Cancer Hospital from January 2018 to January 2023. The study population was divided into two groups: one group received IAIT sequence by systemic standard of care (SOC) therapy group (ISOC; <i>n</i> = 340), while the other group received systemic SOC therapy alone (<i>n</i> = 234). To reduce potential selection bias between the two groups, propensity score matching (PSM) was employed. The primary outcome measured was overall survival (OS). A prognostic model for IAIT was then constructed using five supervised ML models. The performance of the model was assessed by calculating the area under the receiver operating characteristic curve (AUC) and decision curve analysis. Kaplan-Meier analysis was used to reveal the OS risk stratification of the ML. To assess the prognostic nature of our models, we will include interaction terms between treatment modalities and key prognostic factors, followed by likelihood ratio tests to evaluate their significance.</p><p><strong>Results: </strong>After PSM 1:1, 574 patients were divided into two groups. The median OS of patients who received ISOC was significantly higher than those who received systemic SOC therapy alone (40 vs 25 months, <i>p</i> = 0.036). Among the five ML models, the Random Survival Forest model demonstrated the most robust prognostic performance with 1-year, 2-year, and 3-year AUCs of 0.899 (95% confidence interval (CI): 0.858-0.939), 0.903 (95% CI: 0.864-0.943), and 0.873 (95% CI, 0.828-0.919). In the external validation cohort, the AUCs for 1, 2, and 3 years were 0.665 (95% CI: 0.455-0.875), 0.737 (95% CI: 0.636-0.837), and 0.730 (95% CI: 0.640-0.821), respectively. Kaplan-Meier curve analysis confirmed the model's prognostic power for the ISOC treatment strategy. We tested for interaction effects between treatment modalities (e.g., ISOC vs SOC) and the ML model's risk strata, but no significant interaction was observed (<i>P</i> for interaction <i>p</i> > 0.05).</p><p><strong>Conclusion: </strong>In this study, ISOC significantly improved the prognosis of patients. The ML model provides accurate prognostic stratification for uCRLM patients, which may aid in risk-based clinical decision-making.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251353084"},"PeriodicalIF":4.3,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144576327","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":"Clinical landscape for patients with head and neck cancers enrolled in phase I trials at a tertiary referral center.","authors":"Daria Maria Filippini, Raphael Sanchez, Etienne Bastien, Nicolas Jacquin, Alexandro Paccapelo, Caroline Nhy, Jerzy Klijanienko, Valentin Calugaru, Anne Chilles, Wahib Ghanem, Guillaume Rougier, Antoine Dubray Vautrin, Nathalie Badois, Maria Lesnik, Olivier Choussy, Marie Paule Sablin, Christophe Le Tourneau, Grégoire Marret","doi":"10.1177/17588359251337244","DOIUrl":"10.1177/17588359251337244","url":null,"abstract":"<p><strong>Background: </strong>Recent advances in understanding the biology of cancer have resulted in an extensive armamentarium of new therapeutic agents, most often tested on various tumor types at the earliest stages of drug development. However, the clinical impact of these therapies on patients with head and neck cancer (HNC) remains underexplored and requires further evaluation.</p><p><strong>Objectives: </strong>To investigate the clinical outcomes and toxicity profiles of patients with HNC enrolled in phase I trials (Ph1t) at a tertiary referral center over the last decade.</p><p><strong>Design: </strong>A retrospective cohort study was conducted, analyzing data from HNC patients enrolled in phase I trials at the Curie Institute between October 2011 and January 2024.</p><p><strong>Methods: </strong>Data on baseline characteristics, hematologic biomarkers, and outcomes were extracted from medical records. Objective response rate (ORR) and Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were analyzed. A Cox model was used for the identification of prognostic factors.</p><p><strong>Results: </strong>One hundred and thirty patients were enrolled in Ph1t for recurrent/metastatic (R/M) setting (66.9%), including 20.8% of patients being treated with more than two lines of therapy, followed by locally advanced (LA) treated with radical surgery or exclusive chemo/radiotherapy (17.7%), neoadjuvant (10.0%), and adjuvant (5.4%) Ph1t. Patients were treated with immunotherapy (53.8%), targeted therapy (23.1%), bispecific antibody (8.5%), antibody-drug conjugate (4.6%), and other agents (10.0%). In 122 patients evaluable for response, ORR were 16.5%, 87.0%, and 92.3% in R/M, LA, and neoadjuvant Ph1t, respectively. Median PFS/OS rates were 2.0/8.3, 21.5/38.3, and 20.0/27.4 months in R/M, LA, and neoadjuvant Ph1t, respectively.At multivariable analysis, lower lymphocytes (HR = 0.144; 95% CI: 0.052-0.399; <i>p</i> < 0.001) and lower albumin levels (HR = 0.922; 95% CI: 0.879-0.966; <i>p</i> < 0.001) remained associated with poorer OS. Grade 3-4 adverse events were recorded in 27/130 patients (20.8%). The most frequent were hematologic and gastrointestinal disorders. No treatment-related deaths occurred.</p><p><strong>Conclusion: </strong>HNC Ph1t show encouraging results in terms of early efficacy signals and safety profiles, emphasizing their value across a variety of clinical settings.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251337244"},"PeriodicalIF":4.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544972","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}