Cancer Medicine最新文献

{"title":"CO-Rebreathing in Essential Thrombocythemia and Polycythemia Vera. A Revival of an Old Methodology to Improve Diagnosis and Phlebotomy Decisions.","authors":"Hans C Hasselbalch, Morten Kranker Larsen, Lea Løffler, Camilla Andersen, Isabella Davidsen, Mette Grymer Jensen, Jonas Bechlund, Lasse Kjær, Vibe Skov, Henning Bay Nielsen, Carsten Lundby","doi":"10.1002/cam4.72317","DOIUrl":"10.1002/cam4.72317","url":null,"abstract":"<p><p>The diagnostic landscape for the Philadelphia-negative myeloproliferative neoplasms (MPNs), particularly in distinguishing Essential Thrombocythemia (ET) from Polycythemia Vera (PV), is compromised. The gold standard for diagnosing PV-measurement of red cell mass (RCM) by radioisotope dilution-has been largely abandoned, leading to widespread misclassification. Thus, an estimated 30%-50% (varying by diagnostic center and testing practice) of JAK2V617F-positive ET patients may, in fact, have \"hidden\" PV, depriving them of the cornerstone PV therapy: phlebotomy. This diagnostic inaccuracy exposes a sizable patient population to an unfortunate high risk of life-threatening thrombotic events. Concurrently, the management of established PV is suboptimal, often relying solely on hematocrit, a flawed parameter especially in iron-deficient or hydroxyurea-treated patients. This perspective calls for the revival and clinical implementation of the Carbon Monoxide (CO)-rebreathing technique as a promising, rapid, and nonradioactive alternative for RCM assessment. Herein, we review the history of this methodology and discuss its potential to improve MPN care by ensuring precise diagnosis, guiding rational phlebotomy, and ultimately reducing thrombotic morbidity and mortality, while also candidly addressing the current evidentiary and practical limitations that must be resolved before clinical adoption, while also offering potential health-economic benefits.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72317"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101606","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":"Incidence, Clinical Characteristics, Management, and Outcomes of Hematologic Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors: A Single-Center Japanese Retrospective Cohort Study.","authors":"Ryo Yoshimaru, Hirotaka Nakamura, Yong-Mei Guo, Kensuke Matsuda, Tetsuya Sakai, Yoshitaka Zenke, Kiyotaka Yoh, Kohei Shitara, Nobuaki Matsubara, Kenichi Harano, Hiromichi Nakajima, Nobuyuki Takahashi, Masafumi Ikeda, Takao Fujisawa, Saki Nakamura, Kenta Akie, Masayuki Ito, Masashi Wakabayashi, Junichiro Yuda","doi":"10.1002/cam4.72337","DOIUrl":"10.1002/cam4.72337","url":null,"abstract":"<p><strong>Introduction: </strong>Immune-related adverse events (irAEs) are complications associated with immune checkpoint inhibitors (ICIs). Hematologic irAEs (heme-irAEs) are rare but potentially serious and may interfere with cancer treatment. However, their clinical characteristics remain insufficiently described.</p><p><strong>Methods: </strong>We conducted a single-center retrospective study using the National Cancer Center Hospital East medical database from April 1, 2014, to March 31, 2024. Potential heme-irAE cases were identified using diagnostic name searches, bone marrow examination records, and positive DAT results and were followed by chart review to exclude alternative etiologies, such as chemotherapy-related myelosuppression, marrow involvement, infection, and hematologic malignancy.</p><p><strong>Results: </strong>Of the 3371 patients treated with ICI-containing regimens, 40 patients developed heme-irAEs, indicating an observed incidence of 1.2%. The most common heme-irAE reported was immune thrombocytopenia, and 85.0% of these events were Grade 3 or higher. The median time from ICI initiation to heme-irAE onset was 12 weeks. For all affected patients included in the regimen-specific onset-time comparison, the median time to heme-irAE onset appeared shorter with dual ICI therapy without chemotherapy than with ICI monotherapy, although this descriptive comparison was based on a small number of cases. ICI-containing regimens were interrupted or discontinued in most patients, and systemic corticosteroids were administered to 25 patients, 18 of whom achieved hematologic improvement. Cancer treatment was resumed or continued for 20 patients, with no recurrent heme-irAEs observed during the follow-up period. In an exploratory landmark analysis, hematologic response was associated with longer survival after heme-irAE onset.</p><p><strong>Conclusion: </strong>Heme-irAEs were rare but frequently severe in this Japanese single-center cohort. Their occurrence was associated with prolonged interruption of cancer treatment, underscoring the importance of early recognition, careful diagnostic evaluation, and multidisciplinary management of heme-irAEs. Our findings regarding dual ICI therapy, survival, and subsequent ICI therapy after heme-irAE onset should be interpreted as exploratory.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72337"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101693","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":"Advancing Patient-Centred AI With Adaptive Machine Learning.","authors":"Dimitrios Kalogeropoulos, Paul Barach, Andrea Downing, Stefaan Verhulst, Maryam Lustberg","doi":"10.1002/cam4.72371","DOIUrl":"https://doi.org/10.1002/cam4.72371","url":null,"abstract":"<p><p>Healthcare services and data ecosystems remain fragmented, inequitable and misaligned with patient, clinician and public health needs. Three pathways to patient-centred Artificial Intelligence (AI) have emerged to address this: data collaboration, Whole System Approaches and digital inclusion. Each has advanced the field. However, none delivers the continuous, participatory and outcome-grounded learning that equitable AI demands. The populations whose data drives AI learning must also be the populations who benefit from it. This principle has not been structurally embedded in any existing pathway. This narrative review defines a framework for operationalising Adaptive Machine Learning (AML) as a fourth, integrative pathway to patient-centred AI. AML is defined as continuous learning from real-world individual-level data to generate personalised, population-level insights returning direct benefit to the communities who produce them. A narrative review of PubMed and Google Scholar (2018-2025) was conducted across five thematic domains: AI and machine learning in healthcare; real-world data and evidence; patient-centred care and digital health; data governance and AI regulation; and adaptive clinical trial design. Search terms covered healthcare AI applications and adaptive, continuously learning systems, emphasising prediction-oriented rather than static diagnostic approaches. Eligibility was determined through iterative thematic analysis. Eight systemic barriers to patient-centred AI are identified and the three existing pathways critically examined for limitations in addressing bias, validation and equitable implementation. AML is proposed as the mechanism that closes this gap, connecting systems medicine, personalised medicine and precision medicine through continuous, outcome-based learning, identifying three original conceptual contributions as enablers: Integrative Data Governance (IDG), Adaptive Clinical Trial (ACT) designs and Evidence Sandbox Facilities (ESFs). Progress requires globally standardised Healthcare Data Recycling frameworks, adaptive evaluation methodologies and ESFs enabling multi-stakeholder validation. Future research should address federated AML validation, collective consent mechanisms and alignment of regulatory frameworks with international AI governance standards.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72371"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163556","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 Status and Its Association With Patient-Reported Outcomes in Women With Non-Metastatic ER-Positive Breast Cancer Undergoing Adjuvant Endocrine Therapy.","authors":"Danielle Laperche-Santos, Amanda Guimarães Castro Custodio, Fernanda Cesar Moura, Sulene Cunha Sousa Oliveira, Andrea Kazumi Shimada, Renata Arakelian, Heloisa Resende, Anna Luiza Zapalowski Galvão, Bruno Santos Wance de Souza, Monalisa Ceciliana Freitas Moreira de Andrade, Yuri Cardoso Rodrigues Beckedorff Bittencourt, Maria Cristina Figueroa Magalhães, Luciana Castro Garcia Landeiro, Poliana Albuquerque Signorini, Daniela Jessica Pereira, Angélica Nogueira-Rodrigues, Romualdo Barroso-Sousa, Daniele Assad-Suzuki","doi":"10.1002/cam4.72343","DOIUrl":"10.1002/cam4.72343","url":null,"abstract":"<p><strong>Purpose: </strong>To examine associations of body mass index (BMI) with sociodemographic, clinical, treatment-related, psychosocial, and patient-reported outcomes among women with non-metastatic estrogen receptor-positive (ER+) breast cancer receiving adjuvant endocrine therapy.</p><p><strong>Methods: </strong>This multicenter cross-sectional study included 557 women treated at 11 Brazilian public and private institutions from June 2021 to March 2024. Participants were classified as having normal weight, overweight, or obesity. Health-related quality of life was assessed using the EORTC QLQ-C30 and QLQ-BR23. Characteristics were compared across BMI categories using chi-square or Fisher's exact test and Kruskal-Wallis test. Multinomial logistic regression examined factors associated with BMI category, using normal weight as the reference.</p><p><strong>Results: </strong>Of 557 participants, 172 had normal weight, 234 were overweight, and 151 had obesity. Education, comorbidities, hospital type, cancer stage, endocrine therapy, axillary dissection, prior chemotherapy, and radiotherapy differed across BMI categories. Participants with obesity had poorer physical functioning and greater pain. In the final model (n = 554), axillary dissection (OR = 2.51; 95% CI = 1.37-4.59) and continuous medication use (OR = 2.92; 95% CI = 1.78-4.79) were associated with obesity versus normal weight. Tamoxifen was inversely associated with overweight (OR = 0.58; 95% CI = 0.36-0.91), whereas low treatment adherence (OR = 1.54; 95% CI = 1.01-2.35) and continuous medication use (OR = 1.68; 95% CI = 1.10-2.58) were positively associated.</p><p><strong>Conclusion: </strong>Overweight and obesity were common and associated with sociodemographic, clinical, treatment-related, and selected quality-of-life characteristics. These findings support integrated survivorship care addressing weight-related health, comorbidities, functional limitations, and symptom burden. Longitudinal studies are needed to clarify temporal relationships.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72343"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126342","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":"Targeting Integrins in Triple Negative Breast Cancer: Therapeutic Potential of Monoclonal Antibodies, PARP Inhibitors, Synthetic Peptides, and Aptamers.","authors":"Mobina Darabi, Zeynab Zahedi, Kosar Zolfaghari, Alireza Kordi, Kiarash Saleki, Niloufar Yazdanpanah, Nima Rezaei","doi":"10.1002/cam4.72247","DOIUrl":"10.1002/cam4.72247","url":null,"abstract":"<p><p>Triple-negative breast cancers (TNBCs) are associated with poor prognosis and chemoresistance. Recent reports indicate that extracellular matrix (ECM) molecules, such as integrins, could influence TNBC development. Integrins are adhesion macromolecules that modulate ECM characteristics such as stiffening of ECM and being associated with hypoxia. Therefore, dysregulation in integrins could compromise the efficient delivery of cancer treatments. Some peptides and aptamers can directly target integrins, and they are now being studied; however, most monoclonal antibodies and PARP inhibitors that are used for TNBC do not directly target integrins. Integrins and the ECM can change the way these treatments work. Currently, the efficacy of these candidates is still being evaluated, and the majority of studies are in the early phase of development. The present article reviews the role of integrins in cancer development and captures the state-of-the-art evidence on the therapeutic targeting of integrins in breast cancer. Also, solutions to overcome challenges in the field are suggested.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72247"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163324","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":"Targeting the Tumor Microenvironment Network to Overcome Immunotherapy Resistance in Non-Small Cell Lung Cancer: Mechanisms to Clinical Translation.","authors":"Zengrui Wang, Zhuang Luo, Le Wang, Jiefu Tang, Zhi Zhang, Xinli Fan","doi":"10.1002/cam4.72335","DOIUrl":"10.1002/cam4.72335","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy has transformed the treatment landscape for advanced non-small cell lung cancer (NSCLC), yet resistance mediated by the tumor microenvironment (TME) limits its efficacy in most patients. This review aims to synthesize the current understanding of the TME as an integrated network driving immunotherapy resistance and to evaluate emerging therapeutic strategies aimed at overcoming it.</p><p><strong>Methods: </strong>We conducted a comprehensive narrative review of key literature in the field, sourced from PubMed and major conference proceedings. The focus was on mechanistic studies elucidating immunosuppressive cell circuits, metabolic reprogramming, epigenetic regulation, spatial heterogeneity, and microbiome interactions within the lung cancer TME. Preclinical and clinical evidence for TME-targeted combination therapies and biomarker development was also critically analyzed.</p><p><strong>Results: </strong>The TME orchestrates resistance through highly interconnected axes: (1) cellular circuits including myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and M2-polarized tumor-associated macrophages (M2-TAMs), (2) metabolic barriers (lactate acidosis, nutrient depletion), (3) epigenetic reprogramming, and (4) systemic communication via exosomes and the microbiome. Spatial transcriptomics reveals that driver mutations (e.g., EGFR, KRAS) shape distinct immune-excluded architectures. To disrupt this network, rational combination strategies-such as immune checkpoint inhibitors with metabolic modulators (LDHAi), epigenetic drugs, targeted agents (METi), or microbiome interventions-show synergistic potential in early-phase trials. Furthermore, a tiered biomarker system integrating spatial, metabolic, and microbial features is proposed to guide patient stratification.</p><p><strong>Conclusion: </strong>Overcoming immunotherapy resistance requires a paradigm shift from single-target to network-targeted therapy. This review provides an integrated framework for understanding TME-mediated resistance and translates these insights into a roadmap for clinical translation. Future efforts must prioritize biomarker-validated, rationally designed combination therapies to improve outcomes for patients with resistant NSCLC.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72335"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163886","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":"Skeletal Muscle Index, Tumor and Systemic Immunity, and Survival in Advanced Pancreatic Ductal Adenocarcinoma.","authors":"Yue Ma, Ru Jia, Mengjiao Fan, Guochao Deng, Tieqiang Liu, Yanrong Wang, Yue Li, Nan Zhang, Fang Pang, Yue Shi, Yaoyue Zhang, Yuting Pan, Qi Wang, Zhikuan Wang, Guanghai Dai","doi":"10.1002/cam4.72378","DOIUrl":"10.1002/cam4.72378","url":null,"abstract":"<p><strong>Background: </strong>This study investigated relationships between the skeletal muscle index (SMI) and the tumor immune microenvironment (TIME), peripheral immune phenotypes, and serum biomarkers in advanced pancreatic ductal adenocarcinoma (PDAC) and evaluated the prognostic significance of these parameters.</p><p><strong>Methods: </strong>A retrospective analysis of 119 advanced PDAC patients was performed. Sarcopenia was diagnosed using sex-specific SMI cut-offs from baseline L3-level computed tomography (CT) images. The TIME was characterized by multiplex immunofluorescence (mIF; n = 31), peripheral immunity by flow cytometry, and serum biomarkers by routine testing. Associations with SMI were examined using Spearman correlation; prognostic relevance was assessed using Cox proportional hazards models.</p><p><strong>Results: </strong>Sarcopenia (56/119, 47.1%) was associated with shorter progression-free survival (PFS) (8.83 vs. 12.03 months, p = 0.016) and overall survival (OS) (10.20 vs. 17.33 months, p = 0.014). SMI correlated most strongly with stromal CD8⁺ T cells (ρ = 0.52), stromal total T cells (ρ = 0.52), and stromal M2 macrophages (ρ = 0.50) in the TIME; with circulating Th2-like cells (ρ = -0.58) and CD4⁺ memory T cells (ρ = 0.45) peripherally; and with hemoglobin (ρ = 0.32) among serum markers. In multivariable Cox regression, stromal CD4⁺ Treg percentage independently predicted OS (hazard ratio [HR] = 7.60, 95% confidence interval [CI] 1.60-36.22, p = 0.011), stromal CD56dim natural killer (NK)-cell density predicted PFS (HR = 1.015, 95% CI 1.001-1.028, p = 0.031), and the lymphocyte-to-monocyte ratio (LMR) predicted both PFS (HR = 0.86, p = 0.023) and OS (HR = 0.83, p = 0.009). No peripheral lymphocyte subset reached prognostic significance.</p><p><strong>Conclusion: </strong>SMI is broadly associated with local and systemic immune phenotypes in advanced PDAC. Stromal CD4⁺ regulatory T cells (Tregs), CD56dim NK cells, and LMR carry independent prognostic information and may complement body-composition assessment.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72378"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190331","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":"CDS2 Drives Tumor Progression in Epithelial Ovarian Cancer via the PI3K/AKT Pathway.","authors":"Lixue Cao, Yanzhen Chen, Yingqi Liu, Changnian Yang, Zhentao Zhang, Yongqing Lin, Yiyuan Wang, Siman Chen, Fei Yu, Haiyan Ye, Shanshan Wu","doi":"10.1002/cam4.72309","DOIUrl":"https://doi.org/10.1002/cam4.72309","url":null,"abstract":"<p><strong>Background: </strong>Epithelial ovarian cancer (EOC) frequently disseminates within the lipid-rich peritoneal cavity, where tumor progression is accompanied by metabolic adaptations involving lipid utilization and mitochondrial function. Although these metabolic alterations are increasingly recognized as important features of EOC progression and peritoneal metastasis, the molecular factors linking mitochondrial-lipid metabolic remodeling with aggressive tumor behavior remain incompletely characterized. We therefore integrated mitochondrial- and lipid metabolism-related transcriptomic analyses to identify candidate regulators and further investigated the clinical and biological features associated with CDS2.</p><p><strong>Results: </strong>Seven key genes associated with mitochondrial and lipid metabolism were identified in EOC through comprehensive bioinformatic analyses and were used to construct the MALRS prognostic model. Further integration of FIGO stage, histologic grade, and MALRS scores yielded a nomogram whose calibration plots showed good agreement between predicted and observed 1-, 3-, and 5-year survival probabilities. Subsequent screening of these candidate genes in chemotherapy-resistant datasets identified CDP-diacylglycerol synthase 2 (CDS2) as the most consistently upregulated candidate gene. Clinical validation confirmed that CDS2 was significantly overexpressed in tumor tissues and was associated with advanced disease stage, and survival analysis showed that higher CDS2 expression was associated with shorter progression-free survival (PFS) in stage III/IV patients. Functional characterization demonstrated that CDS2 overexpression promoted both lipid droplet accumulation and migratory capacity in ovarian cancer cells. Pathway analysis identified significant enrichment of PI3K/AKT signaling, and experimental validation confirmed CDS2-mediated hyperactivation of PI3K/AKT phosphorylation. Computational immune-deconvolution analyses further identified exploratory associations between CDS2 expression, estimated T-cell abundance, and immune-checkpoint transcripts.</p><p><strong>Conclusion: </strong>CDS2 is a lipid metabolism-associated candidate biomarker linked to aggressive clinicopathological features in EOC. Our findings associate CDS2 with disease progression, PI3K/AKT-related signaling, and immune-related transcriptomic features, supporting its further evaluation as a candidate prognostic marker.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72309"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149222867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of PD-1/PD-L1 Inhibitors Combined With Anti-Angiogenic Tyrosine Kinase Inhibitors for Recurrent or Metastatic Nasopharyngeal Carcinoma: A Systematic Review and Single-Arm Meta-Analysis.","authors":"Rongyi Hu, Tiebin Li, Ziman Luo, Huining Chen, Song Qu","doi":"10.1002/cam4.72340","DOIUrl":"10.1002/cam4.72340","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the efficacy and safety of PD-1/PD-L1 inhibitors plus small-molecule anti-angiogenic drugs (apatinib, anlotinib and famitinib) for recurrent/metastatic nasopharyngeal carcinoma (R/M NPC).</p><p><strong>Methods: </strong>Systematic searches of major databases up to January 7, 2026 identified prospective single-arm Phase II trials and retrospective cohort/real-world studies of PD-1/PD-L1 inhibitors combined with apatinib, anlotinib, or famitinib in R/M NPC. Pooled response and safety rates were estimated using random-effects models, with study quality assessed by appropriate tools.</p><p><strong>Results: </strong>Nine studies comprising 10 independent cohorts (357 patients) were included. The pooled objective response rate (ORR) was 48% (95% CI: 39%-57%), the disease control rate (DCR) 83% (95% CI: 77%-88%), and the 1-year overall survival rate 79% (95% CI: 68%-86%). The incidence of grade ≥ 3 treatment-related adverse events (TRAEs) was 47% (95% CI: 37%-58%). The most frequent serious TRAEs were hypertension (9%), hand-foot syndrome (10%), and nasopharyngeal necrosis (14%), with the latter requiring close monitoring due to its potential for severe bleeding complications. No treatment-related deaths were reported across all included studies. Subgroup analysis showed no significant difference in ORR between camrelizumab and toripalimab; apatinib yielded higher ORR than anlotinib; immunotherapy-naive patients had significantly higher ORR than those previously treated with immune checkpoint inhibitors (ICIs) (p = 0.0028).</p><p><strong>Conclusion: </strong>The combination shows promising antitumor activity and a generally acceptable safety profile in R/M NPC, particularly for immunotherapy-naive patients. These findings support further investigation in well-designed randomized controlled trials, but confirmation of its role relative to standard therapies requires larger comparative studies.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72340"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079399","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":"Increased Lymphocyte Proportions as a Candidate Biomarker for Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitors and Chemotherapy.","authors":"Nanami Ito, Yoshihiko Tasaki, Yosuke Sugiyama, Takehiro Uemura, Keisuke Yokota, Ryo Ogawa, Takaya Shimura, Daisuke Kawakita, Yumi Wanifuchi-Endo, Yoshihisa Mimura, Moeko Iida, Kunihiro Odagiri, Yuka Kimura, Misato Tomita, Yuji Hotta, Tatsuya Toyama, Shinichi Iwasaki, Hiromi Kataoka, Shuji Takiguchi, Katsuhiro Okuda, Akio Niimi, Yoko Furukawa-Hibi","doi":"10.1002/cam4.72361","DOIUrl":"10.1002/cam4.72361","url":null,"abstract":"<p><strong>Background: </strong>Combination therapy comprising immune checkpoint inhibitors (ICIs) and chemotherapy is standard treatment for many cancer types. However, the management of adverse events (AEs) induced by combination therapy is more complicated than that of AEs induced by ICI monotherapy. Although immune-related AEs (irAEs) induced by ICIs and AEs induced by chemotherapy require distinct therapeutic approaches, distinguishing between them can be challenging. Therefore, in this exploratory study, we aimed to investigate whether lymphocyte proportion could serve as a candidate biomarker associated with the occurrence of irAEs in patients receiving ICI plus chemotherapy combination therapy.</p><p><strong>Patients and methods: </strong>We categorized 122 patients into the irAE group (those who experienced irAEs), chemo-AE group (those with chemotherapy-induced AEs), and non-AE group (those without AEs) and analyzed their lymphocyte proportions before one course (baseline sample) and two courses (two-course sample) of treatment.</p><p><strong>Results: </strong>Lymphocyte proportions of the baseline samples did not differ between the non-AE, chemo-AE, and irAE groups. The lymphocyte proportion of the two-course sample of the irAE group was significantly higher than that of the non-AE group (25.8% vs. 21.9%; p < 0.05). The lymphocyte proportion of the two-course sample of the irAE group was significantly higher than that of the chemo-AE group (25.8% vs. 19.6%; p < 0.05). The multivariate logistic regression analysis showed that a lymphocyte proportion ≥ 23.9% in the two-course sample significantly increased the risk of irAEs (odds ratio = 3.04; p < 0.05).</p><p><strong>Conclusions: </strong>An increased lymphocyte proportion before the two courses of treatment was associated with the occurrence of irAEs and may serve as a candidate biomarker.</p>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"15 10","pages":"e72361"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101655","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}